Reptiles tend to have a broad innate immune response followed by a more moderate adaptive response, and as an ectotherm, their immune response is strongly affected by temperature. The innate immune responses in reptiles encompass a diverse group of molecules and cells that includes non‐specific leukocytes, lysozymes, antimicrobial peptides, the complement pathway and fever. The adaptive response involves both T and B cells; however, reptile humoral responses are much less robust than mammalian responses. Thus, reptiles may rely more heavily on a natural antibody response. The slower adaptive response may be because reptiles lack lymph nodes and do not form germinal centres. Phagocytic B cells have also been identified in reptiles. Studies of the reptilian immune system may contribute to our understanding of the evolution of the immune system as well as to the fields of conservation biology, ecological immunology and human medicine. Key Concepts Reptiles have a broad innate immune response able to encompass a variety of pathogens followed by a specific adaptive response. Because reptiles are ectothermic, temperature has a strong effect on immune responses. Seasonal variation in structure and function of the immune system in reptiles is common. As the only ectothermic amniotes, reptiles provide vital information on the evolution of the immune systems.