Plastic pipes used to convey hot and cold drinking water are synthetic polymers containing numerous additives that enhance durability, impact strength, and toughness, and resist material degradation. Although some research studies have been conducted to evaluate the type and levels of chemical substances migrating from polymeric materials into drinking water, the potential adverse health effects associated with these compounds in potable water have not been described. This review evaluates the literature on the occurrence of regulated and unregulated substances in drinking water related to the use of plastic pipes, characterizes potential health hazards, and describes uncertainties associated with human health and exposure in need of further research. Of particular public health concern is the potential for sensitive populations to be exposed to short-term elevations in leachates during critical periods, and for co-occurring leachates targeting the same organ(s) and/or sharing a common mode of toxic action to have additive or synergistic effects. Contaminants are measured in the distribution system, not at the tap where human exposure actually occurs. For increased health protection, it is important to identify compounds that migrate from plastic pipes into drinking water and to better quantify human exposures and health hazards to these substances and their degradates.