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 food-borne 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 water-borne 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 variability, and regional differences, in pathogen and indicator organism concentrations in water; direct and circumstantial evidence for contaminated water as a source of food-borne 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.