Why do humans have anatomical variations and anomalies? This chapter provides the theoretical background to address this question, which is crucial to pave the way for a more holistic approach to human anatomy and human evolution. In particular, we discuss how this question is being addressed within a growing new subfield of biology, Evolutionary Developmental Pathology (Evo-Devo-Path). Evo-Devo-Path includes more traditional lines of research such as those included in Evolutionary Developmental Biology (Evo-Devo), but also pays special attention to data obtained from chordate comparative, developmental, and evolutionary anatomy and from the direct study of normal/abnormal development of humans, other primates, and other organisms, with a special focus on so-called “natural mutants”. Within this theoretical discussion, we will explain the differences between a so-called “normal” or typical configuration, polymorphisms, variations, and anomalies, and explain why having a more holistic approach to these different types of conditions can help physicians and surgeons, medical students, biologists, and anthropologists better understand where the structures of our body come from, and why they are as they are.