The magazine targeted men ages 21–40 years and featured in-depth articles on fitness, nutrition, and sports, as well as sex tips, fashion advice, interviews, recipes, and surveys.

People who appeared on its cover include Pamela Anderson, Arnold Schwarzenegger, Mark Wahlberg, Liam Hemsworth, Andy Roddick, Joe Weider, Robert Marting, Dana White, Sebastian Siegel, Reggie Bush, Albert Pujols, Karen McDougal, Mike 'The Situation' Sorrentino, Carmen Electra, Tim Tebow, Tom Brady, and John Cena.

Tennis champion Andy Roddick complained when he discovered his body had been altered in the May 2007, cover photo of the magazine.

[7] In October 2011, Men's Fitness gained negative publicity across the internet after publishing an article written by Jordan Burchette.

[8] In the article, candid and unflattering photos of costumed attendees at New York Comic Con were shown alongside seemingly mean-spirited captions.