© 2015 Elsevier Ltd. Cryptosporidium is a parasite responsible for widespread disease in livestock and humans. Recent phylogenetic reclassification of Cryptosporidium from a coccidian to a gregarine dictates an urgent need to reconsider the biology and behavior of this parasite. Overwhelming data now confirm that, like its close relatives, Cryptosporidium is a facultatively epicellular apicomplexan that is able to multiply in a host cell-free environment. We complement the latest phylogenetic and taxonomic proposals with advances in our understanding of Cryptosporidium's biology, with particular focus on in vitro studies that have characterized the development of Cryptosporidium stages in the absence of host cells. Opportunities to revisit in vivo infections are discussed and questions about the Cryptosporidium host cell-free life cycle that remain unanswered highlighted. Cryptosporidium is a widespread yet neglected human and livestock pathogen.The re-emergence of Cryptosporidium as a life-threatening opportunistic pathogen in children in developing countries highlights an urgent need for effective anticryptosporidial therapies.Based on recent genetic analyses, Cryptosporidium is no longer considered a coccidian and has been reclassified as a gregarine, within the subclass Cryptogregaria.Like the gregarines, Cryptosporidium exhibits plasticity in both its life cycle and options for parasitism, including the ability to multiply without host cell encapsulation.The ability of Cryptosporidium to replicate in host cell-free systems such as aquatic biofilms poses a previously unconsidered environmental risk in the spread of disease.