From Jamie Foxx's serenade to Caitlyn Jenner's rousing speech, here's a look at highlights of the annual sports ceremony dating back to its 1993 debut.
THR rounds up some of the ceremony's best moments before 15-time WWE world heavyweight champion John Cena takes the stage at Los Angeles' Microsoft Theater to host the 2016 ESPY Awards this Wednesday.
The longtime college basketball coach, who famously led NC State University to victory in the 1983 NCAA tournament, was honored with the inaugural Arthur Ashe Courage Award at the very first ESPYs in 1993. Valvano, who had been diagnosed with bone cancer in 1992, received a standing ovation for his poignant speech about setting goals and living life to the fullest.
"To me, there are three things we all should do every day. We should do this every day of our lives. Number one is laugh. You should laugh every day. Number two is think. You should spend some time in thought. Number three is you should have your emotions moved to tears, could be happiness or joy," he said. "But think about it. If you laugh, you think and you cry, that’s a full day. That’s a heck of a day. You do that seven days a week, you’re going to have something special."
During his time at the podium, he also announced the creation of The V Foundation for Cancer Research, an endeavor he launched in partnership with ESPN. He ended his speech by saying, "Cancer can take away all my physical abilities. It cannot touch my mind, it cannot touch my heart and it cannot touch my soul. And those three things are going to carry on forever."
Though Valvano vowed to fight his illness and return to the ESPYs stage to honor the following year's Arthur Ashe recipient, he lost his battle to cancer shortly after giving his speech.
Oscar-winning actor Poitier gave a moving introductory speech before presenting the late boxing legend with the Arthur Ashe Courage Award in 1997.
"The first thing I remember is his voice. Back then, I thought it was just loud. I didn’t hear the sound of passion and strength. As the years went by, I learned to pay attention to the words he was saying and the conviction behind them," Poitier said at the podium. "In an age of discrimination, he stood up for racial pride. In an era of lost values, he had a spiritual rebirth. In a time of war, Muhammad Ali spoke of peace. When he refused to fight in Vietnam, he paid a price emotionally, financially and professionally. But isn’t that what courage is all about? The willingness to fight for what one believes and for what is right — no matter what the cost."
Foxx served as ESPYs host in 2003 and 2004 and proclaimed his love for the Wimbledon champion with a soulful serenade at both awards shows. He debuted his R&B love song titled "Can I Be Your Tennis Ball?" in 2003 and performed a remix of the track the following year, crooning lyrics like "Don’t you know you look so fine / Whoever you’re seeing, his tennis racket ain't big as mine."
The highlight? Williams joined Foxx onstage and spanked him with a heart-shaped racket (leaving Tom Cruise and LeBron James in a fit of laughter).
Destiny's Child (with members Beyonce, Kelly Rowland and Michelle Williams) brought their 2004 hit to the ESPYs stage with a choreography-laden performance that featured special appearances by track and field star Allyson Felix and Serena Williams.
Timberlake proved himself to be the ultimate entertainer when he put on a one-man show as host of the 2008 ceremony, singing, dancing and rapping to a made-up song that infused jazz, hip-hop, reggae and gospel music.
Ferrell embodied the golf pro when he accepted the best male athlete award on behalf of Woods, who was given the honor for the fourth time.
"People are always asking me, 'Tiger, how do you do it?' And my answer is, 'Shut up.' I ask the questions around here. I’m Tiger Woods," Ferrell joked onstage. "All I did was purposely sever my ACL and broke a bone in my leg, and you know what? I still won the U.S. Open. And that's when even I started to believe it's undeniable, I am the greatest."
He concluded his speech, "What can I say? I’m the best. In your face. Goodnight everybody."
The legendary musician introduced the nominees for 2009's best team award with a short piano tune before proceeding to open the envelope and joking, "Let me see if I can read this." Reading the winner in Braille, Wonder presented the ESPY award to the Los Angeles Lakers.
Anthony Robles, who was born without a right leg, was a two-time winner during the ESPYS when he received the Jimmy V award for perseverance and best male athlete with a disability. Jay Leno presented the award to the athlete for overcoming obstacles that eventually led him to winning the 2010-2011 NCAA wrestling title in a perfect 36-0 season when he attended Arizona State university.
"Every soul who comes to earth with a leg or two at birth must wrestle his opponents knowing it's not what is, it's what can be that measures worth. Make it hard, just make it possible and through pain I'm not complain. My spirit is unconquerable, fearless I will face each foe, for I know I am capable. I don't care what's probable, through blood, sweat, and tears, I am unstoppable," said Robles in his speech.
After being diagnosed with Alzheimer's, the late University of Tennessee women's basketball coach accepted the Courage award from Peyton Manning, and gave an emotional speech on her battle against the disease.
"I've always said you win in life with people. And I have been so blessed to have great people in my life. My son Tyler and I appreciate all of your support. And during this time, that's the next challenge for me and Tyler. And it is time to fight. As I ask all of you to join me together so we will win."
"And I can tell you, tonight I am deeply touched as all of you heard my story," Summitt concluded at the end of her speech. "I am gonna keep on keeping on, I promise you that. Thank you."
Summitt passed away last month. She was 64.
Jon Hamm opened the 20th annual ESPYS by taking shots at multiple athletes including Dwight Howard for his brief stint with the Lakers.
"Dwight Howard recently announced he was leaving the Lakers to play ..." Hamm said before trailing off beneath a cascade of boos from the stands. "You guys heard? Leaving the Lakers to play for the Houston Rockets, which is ... you know ... he's leaving L.A. So I guess it looks like he finally found a way to help the Lakers win."
The Miami Heat, Ray Allen, Alex Rodriguez, Metta World Peace and Ryan Lochte were all placed on the hot seat by Hamm. He also joked about Chris Bosh being fined in game four of the NBA finals back in 2013.
"Chris Bosh recently got fined $5000 for flopping, while Johnny Depp just got paid $20 million for flopping."
When Drake hosted the ESPYS, he couldn't resist calling out Lance Stephenson for blowing in LeBron James' ear during the NBA playoffs.
"I know the truth — you only blow into people's ear whom you truly respect," Drake said, before he kneeled down to reenact the moment and blow in Stephenson's ear himself. The moment was shot in a "kiss cam" moment which was renamed the "Lance Cam."
In one of her first major appearances since transitioning to a woman, former Olympic gold medalist Caitlyn Jenner spoke on equal rights for the transgender community. The Olympic Gold medalist accepted the Arthur Ashe Courage award at the ESPYS, and proceeded thanked her family, and her "buddy" Diane Sawyer whom she gave a revealing interview to that year about her gender transition.
"This transition has been harder on me than anything I could have imagined," she said. "Trans people deserve something vital: They deserve your respect."
"If you want to call me names, make jokes, doubt my intentions, go ahead because the reality is, I can take it," said Jenner. "But for the thousands of kids out there who are coming to terms with being true to who they are, they shouldn’t have to take it."