Laboratory studies of pathogens aim to limit complexity in order to disentangle the important parameters contributing to an infection. However, pathogens rarely exist in isolation, and hosts may sustain co-infections with multiple disease agents. These interact with each other and with the host immune system dynamically, with disease outcomes affected by the composition of the community of infecting pathogens, their order of colonization, competition for niches and nutrients, and immune modulation. While pathogen-immune interactions have been detailed elsewhere, here we examine the use of ecological and experimental studies of trypanosome and malaria infections to discuss the interactions between pathogens in mammal hosts and arthropod vectors, including recently developed laboratory models for co-infection. The implications of pathogen co-infection for disease therapy are also discussed.