Parasites account for a significant burden of disease today, with 200 million people infected with malaria and more than 1.5 billion people infected with soil-transmitted helminths alone. This chapter explores the impact that parasitic infection has had on the evolution of Homo sapiens, as well as the impact that our species has had on the evolution of common parasites. It first establishes the long co-evolutionary history that exists between many parasite species and hominins by presenting both direct archaeological evidence for parasitic infection in humans from the Palaeolithic through to modern day, as well as indirect evidence that has been used to identify parasites that were likely passed down from hominin ancestors. It explores the major changes in parasite disease burden through our evolution as a result of biological, cultural and social changes. After establishing the significant time depth to human-parasite interactions it explores the co-evolutionary relationship between humans and their parasites by drawing on recent evidence gained from studies in immunology and genetics, identifying mechanisms that parasites use to alter human immune function to their benefit, human genes involved in parasite resistance and the intricate relationship between autoimmune diseases and parasitic infection. Finally, it reflects on how an evolutionary approach to parasitic infection can contribute to new approaches to the control of parasite transmission and treatment development.