There has been a recent shift in the literature on mosquito/Plasmodium interactions with an increasingly large number of theoretical and experimental studies focusing on their population biology and evolutionary processes. Ecological immunology of mosquito-malaria interactions – the study of the mechanisms and function of mosquito immune responses to Plasmodium in their ecological and evolutionary context – is particularly important for our understanding of malaria transmission and how to control it. Indeed, describing the processes that create and maintain variation in mosquito immune responses and parasite virulence in natural populations may be as important to this endeavor as describing the immune responses themselves. For historical reasons, Ecological Immunology still largely relies on studies based on non-natural model systems. There are many reasons why current research should favour studies conducted closer to the field and more realistic experimental systems whenever possible. As a result, a number of researchers have raised concerns over the use of artificial host-parasite associations to generate inferences about population-level processes. Here I discuss and review several lines of evidence that, I believe, best illustrate and summarize the limitations of inferences generated using non-natural model systems.