The show consists of a daily Trending Now top 5 video countdown that showcases the biggest viral videos of the day on YouTube. Throughout the week, different segments feature musical performances, packages featuring curated lists of videos on YouTube, and interviews with high profile celebrities and YouTube talent. Guests have included will.i.am, Larry King, Mark Cuban, Lisa Kudrow, Stan Lee, Kevin Smith, Jason Mewes, Burnie Burns, Drew Carey, iJustine, Spoken Reasons, Cimorelli, Kendrick Lamar, Talib Kweli, Big Sean, Jenna Marbles, Tony Hsieh, Dustin Lance Black, Jon Landeau, The Gregory Brothers, Antoine Dodson, Incubus, George Takei, Orlando Jones, Riff Raff, Skylar Grey, Danny Trejo, Felicia Day, Paul Scheer, Gilbert Gottfried, Cody Simpson, Snoop Dogg, Jon M. Chu, T.J. Miller, John Cena, Shaquille O'Neal, Billy Corgan, Robert Rodriguez, Common, Chris Hardwick, Margaret Cho, Eve, Russell Simmons, Bobak Ferdowsi, Adam DeVine, Anders Holm, Blake Anderson, Dominic Monaghan, Pentatonix, Romany Malco, Mia Rose, Chelsea Kane and Greg Grunberg.
What's Trending has worked in conjunction with MTV's O Music Awards as well as the American non-profit organization The Trevor Project to stream their yearly event. Actor Daniel Radcliffe participated in a live chat on the show discussing The Trevor Project.
What's Trending has conducted interviews with Arnold Schwarzenegger, while promoting his autobiography, Total Recall: My Unbelievably True Life Story, and was one of the first news outlets to interview Bobak Ferdowsi after the successful launch of the Curiosity rover.
In December 2012, What's Trending participated in the first "Tube-A-Tweet-A-Thon". People would go to Twitter and tweet using the hashtag #Tubeathon and $1 would be donated to Covenant House to try and raise $50,000 to serve homeless youth.
On June 17, 2013, Bedrocket Media Ventures made a seven figure investment in the series.
On June 7, rapper/producer Lupe Fiasco was interviewed during the program and said, "My fight against terrorism, to me, the biggest terrorist is Obama in the United States of America." On June 20, Lupe Fiasco appeared on the Fox News show The O'Reilly Factor defending his comments.
On September 10, 2011 CBS News ended its relationship with Lazar and the show after a tweet was posted by a junior staffer claiming Apple co-founder Steve Jobs had died. A formal apology was issued live at the beginning of the September 13 show, Now the show carries on independently through partnerships with Ustream and Livestream. Marc Hustvedt of Tubefilter wrote, "The show itself is still groundbreaking, and arguably the most polished half-hour live show on the internet right now. It brings intelligent people together to talk about top news stories in an informative way."
In mid-2012, the show rebranded itself and became a daily show covering the most popular videos on YouTube.
In 2014, HLN announced a development deal with What's Trending. Also in 2014, Marriott announces What's Trending as part of their development studio slate. As part of that partnership, Marriott celebrated its Millionth Mobile check-in with Lazar and Jeana Smith, founder of Prank vs Prank. Marriott would later announced a new series, in partnership with What's Trending, titled Experiences.
What's Trending partnered with Samsung to provide live coverage from the Consumer Electronics Show in January 2015, as well as South by Southwest in March.
Also in 2015, What's Trending announced a new COO in James Haffner, who most recently acted as an executive producer for DeFranco Creative.