Risk factors for waterborne enteric infections are deduced primarily from outbreak surveillance data; however, in the United States, only a fraction of the estimated water-related outbreaks are reported through passive surveillance. In the past several years, advances in molecular detection techniques have furthered our knowledge about foodborne and waterborne causes of gastroenteritis, allowing the association of certain pathogens with biologic and exposure-related susceptibilities in their hosts. This article summarizes some of the recent data characterizing susceptibility to three common waterborne pathogens:Cryptosporidium, a protozoan; Norwalk-like virus; and the bacterium Escherichia coli O157:H7. The infectious dose of Cryptosporidium varies by several orders of magnitude by strain, and repeated low-level exposure in drinking water may be protective. Some people may be innately immune to Norwalk-like virus, despite multiple exposures. A major risk factor for E. coli O157:H7 infection is exposure to shallow groundwater sources contaminated with animal waste.