Purpose of Review: Cryptosporidium spp . (C. hominis and C. parvum) are a major cause of diarrhea-associated morbidity and mortality in young children globally . While C. hominis only infects humans, C. parvum is a zoonotic parasite that can be transmitted from infected animals to humans . There are no treatment or control measures to fully treat cryptosporidiosis or prevent the infection in humans and animals . Our knowledge on the molecular mechanisms of Cryptosporidium-host interactions and the underlying factors that govern infectivity and disease pathogenesis is very limited . Recent Findings: Recent development of genetics and new animal models of infection, along with progress in cell culture platforms to complete the parasite lifecycle in vitro, is greatly advancing the Cryptosporidium field . Summary: In this review, we will discuss our current knowledge of host-parasite interactions and how genetic manipulation of Cryptosporidium and promising infection models are opening the doors towards an improved understanding of parasite biology and disease pathogenesis.