Muscle & Fitness has a more mainstream fitness & bodybuilding lifestyle focus than its companion publication, Flex, which mainly covers more specialised "hardcore" and professional bodybuilding topics. It offers many exercise and nutritional tips, while at the same time advertising a variety of nutritional supplements from companies such as Bio-Engineered Supplements & Nutrition.
Muscle & Fitness has also featured actors, natural bodybuilders, athletes and sports personalities such as: Arnold Schwarzenegger, 50 Cent, Evander Holyfield, Joe Weider, Dwayne Johnson, Jean-Claude Van Damme, Muhammad Ali, Emilien De Falco, Lawrence Leritz, Maryse Ouellet, Mike O'Hearn, Matt Kroc, and the March 2006 issue featured WWE chairman Vince McMahon and son in-law Triple H. Triple H also featured in another issue at the end of 2009 and early 2015 with his wife, and Vince's daughter, Stephanie McMahon. It also features a number of figure competitors such as Davana Medina, Jenny Lynn, Monica Brant. In February 2008, the issue also covered former UFC Heavyweight Champion Brock Lesnar, with Muscle and Fitness placing a lot of emphasis on wrestlers and mixed-martial artists towards the end of 2009 and into 2010. Editions included WWE star John Cena, former WWE wrestlers "Stone Cold" Steve Austin and John Morrison, and UFC fighters Todd Duffee and Nate Marquardt. In 2015, 69-year-old Vince again appeared on the cover.
In its December 2015 issue, Muscle & Fitness named Dwayne Johnson its "Man of the Century," crediting him for being "emblematic" of the growth of the fitness industry. Johnson said in the issue "During the lowest point of my life, this magazine was my rock."
There is also a companion magazine called Muscle and Fitness Hers oriented toward women.