Forks Over Knives examines the profound claim that most, if not all, of the degenerative diseases that afflict us can be controlled, or even reversed, by rejecting our present menu of animal-based and processed foods.

Through an examination of the careers of American physician Caldwell Esselstyn and professor of nutritional biochemistry T. Colin Campbell, Forks Over Knives suggests that "most, if not all, of the degenerative diseases that afflict us can be controlled, or even reversed, by rejecting our present menu of animal-based and processed foods." It also provides an overview of the 20-year China-Cornell-Oxford Project that led to Professor Campbell's findings, outlined in his book, The China Study (2005) in which he suggests that coronary disease, diabetes, obesity, and cancer can be linked to the Western diet of processed and animal-based foods (including all dairy products).

With regard to describing the nutritional approach as a "whole foods plant-based" rather than "vegan" one in the film, Director Lee Fulkerson (in an interview with Canada's National Post) notes that, " 'Veganism just means anything that doesn't have animal-based products in it. But you can still eat highly processed foods that are vegan,' he says, citing potato chips and french fries as examples. 'You want to use minimally processed things.' '