Cryptosporidiosis, the disease caused in humans by the opportunistic parasite Cryptosporidium parvum, is the result of zoonotic or anthroponotic transmission. Molecular characterization of different isolates from humans and other mammalian species has recently shown this species to be heterogeneous; this heterogeneity has been linked to the host of isolation, suggesting that the parasites causing zoonotic cryptosporidiosis and those propagated by anthroponotic transmission are genetically distinct. Here, Fatih Awad-El-Kariem provides an update on the taxonomic and epidemiological significance of these observations, and discusses evidence for and against the clonality hypothesis as a model to explain strain variation in this species.