The tenets of the Paleo diet are based on the principle that we are optimally adapted to eat a diet mimicking that of our paleolithic ancestors. However, as the Paleo Movement grows, this paradigm is being met with valid criticism, highlighting the limitations of framing an optimal human diet based purely on an ancestral template. With a few notable exceptions, the Paleo Diet still stacks up when viewed through the lens of contemporary biology, physiology and biochemistry. But, when faced with discord between paleoanthropological evidence and our understanding of the cellular and molecular interactions between an individual food compound and the human body, which rationale wins out? As the Paleo template evolves to reflect advances in nutritional and health sciences, the continued success of the Paleo movement has become reliant on a shift in our lexicon, promoting a more inclusive discourse on the fundamental properties of the healthiest diets.