There is increasing evidence that consumption of raw fresh produce is a major factor contributing to human gastrointestinal illness. A wide variety of pathogens contribute to foodborne illnesses, including bacteria (e.g., Salmonella, pathogenic Escherichia coli), protozoa (e.g., Cryptosporidium, Giardia), and viruses (e.g., noroviruses). Large-scale production of produce typically requires some form of irrigation during the growing season. There is a rapidly growing body of research documenting and elucidating the pathways of produce contamination by waterborne pathogens. However, many gaps still exist in our knowledge and understanding. The purpose of this review is to provide a comprehensive approach to the issue, including the most recent research. Topics covered include temporal and spatial variabilities, and regional differences, in pathogen and indicator organism concentrations in water; direct and circumstantial evidence for contaminated water as a source of foodborne pathogens; fate and transport of pathogens and indicator organisms in irrigation systems, and the role of environmental microbial reservoirs; and current standards for irrigation water quality and risk assessment. A concerted effort by researchers and practitioners is needed to maintain food safety of fresh produce in an increasingly intensive food production system and limited and declining irrigation water resources.