Technical Abstract: Hepatitis E Virus and Cryptosporidium are waterborne pathogens, each consisting of distinct taxa, genotypes, and isolates that infect humans, nonhuman animal species, or both. Some are associated with disease, others are not. Factors contributing to disease are extremely complicated, possibly involving differences in one or more traits associated with an organism's taxon, genotype, or isolate and its infectious dose, and age or condition, as well as the host's physiology and immune status. Potential virulence factors have not yet been identified for HEV. Putative virulence factors for Cryptosporidium might be found in recently recognized genes involved in processes such as excystation, adherence to host cells, invasion, intracellular maintenance, and host cell destruction.