Immunoglobulin M (IgM) is an ancient antibody class that is found in all vertebrates, with the exception of coelacanths, and is indispensable in both innate and adaptive immunity. The equally ancient human malaria parasite, Plasmodium falciparum, formed an intimate relationship with IgM with which it co-evolved. In this article, we discuss the association between IgM and human malaria parasites, building on several recent publications that implicate IgM as a crucial molecule that determines both host and parasite survival. Consequently, a better understanding of this association may lead to the development of improved intervention strategies.