Preservation of water quality and prevention of waterborne disease is a complicated task requiring a coordinated effort from many diverse disciplines including physicians, healthcare providers, epidemiologists, microbiologists, academic scientists, science researchers, local and national health authorities, public and environmental health specialists, water engineers and water purveyors. Any successful strategy to ensure water quality and safety in the United States must include the medical community as a valued stakeholder and active participant in this ongoing public health challenge. Unfortunately, the majority of practicing healthcare providers in the US has received limited training in the recognition and evaluation of water-related disease and faces many significant challenges and numerous barriers to diagnosing waterborne disease and the health effects of water pollution in their patients. The purpose of this review is to define the specific challenges facing the medical community with regard to clinical recognition of water-related disease and to provide recommendations for the development of specialized clinical resources and targeted educational outreach programs to assist the medical community in improving their ability to appropriately address water-related disease in their patients.