Cryptosporidiosis is now recognized as one of the most common human enteric infections. In this critical review, relatively unexplored details of transmission, the interaction with malnutrition and the development of chronic diarrhea, and the need far effective treatment are highlighted. Our inability to detect small numbers of food-borne oocysts limits our understanding of this transmission route, and the possibility of respiratory transmission is yet to be rigorously studied. The toll this disease imposes on children, especially the malnourished, has not been fully appreciated. Indeed, the dynamics of the progression from acute cryptosporidiosis to chronic diarrhea and death of malnourished children is still enigmatic. Our knowledge of the intestinal pathophysiology, while limited, is increasing. The lack of effective drug therapy is both remarkable and sobering. Overall, these unknown areas demonstrate how little we truly know about this parasite.