Ixodes ticks maintain a large and diverse array of human pathogens in the enzootic cycle, including Borrelia burgdorferi and Babesia microti. Despite the poor ecological fitness of B. microti, babesiosis has recently emerged in areas endemic for Lyme disease. Studies in ticks, reservoir hosts and humans indicate that coinfection with B. burgdorferi and B. microti is common, promotes transmission and emergence of B. microti in the enzootic cycle, and causes greater disease severity and duration in humans. These integrative studies may serve as a paradigm for the study of other vector-borne coinfections. Identifying ecological drivers of pathogen emergence and host factors that fuel disease severity will help guide the design of effective curative and prevention strategies.