Cryptosporidium: species are protozoan parasites that are important causes of diarrheal disease including waterborne outbreaks, childhood diarrhea in resource-poor countries, and diarrhea in compromised hosts worldwide. Recent studies highlight the importance of cryptosporidiosis in childhood diarrhea, malnutrition, and death in resource-poor countries. Despite this, only a single drug, nitazoxanide, has demonstrated efficacy in human cryptosporidiosis and its efficacy is limited in malnourished children and patients with HIV. Areas covered: In this review, we highlight work on potential targets for chemotherapy and review progress on drug development. A number of new targets have been identified for chemotherapy and progress has been made at developing drugs for these targets. Targets include parasite kinases, nucleic acid synthesis and processing, proteases, and lipid metabolism. Other groups have performed high-throughput screening to identify potential drugs. Several compounds have advanced to large animal studies. Expert opinion: Development of drugs for cryptosporidiosis has been plagued by a lack of success. Barriers have included poor correlations between in vitro activity and clinical success as well as frequent unanticipated adverse effects. Without a clear pathway forward, it is wise to maintain a diverse development pipeline. Drug developers should also realize that success will likely require a sustained, methodical effort.