Ten years ago, ‘Understanding the vertebrate immune system: insights from the reptilian perspective’ was published. At the time, our understanding of the reptilian immune system lagged behind that of birds, mammals, fish and amphibians. Since then, great progress has been made in elucidating the mechanisms of reptilian immunity. Here, I review recent discoveries associated with the recognition of pathogens, effector mechanisms and memory responses in reptiles. Moreover, I put forward key questions to drive the next 10 years of research, including how reptiles are able to balance robust innate mechanisms with avoiding self-damage, how B cells and antibodies are used in immune defense and whether innate mechanisms can display the hallmarks of memory. Finally, I briefly discuss the links between our mechanistic understanding of the reptilian immune system and the field of eco-immunology. Overall, the field of reptile immunology is poised to contribute greatly to our understanding of vertebrate immunity in the next 10 years.