Produced water is a chemically complex waste stream generated during oil and gas development. Roughly four trillion liters were generated onshore in the United States in 2021 (ALL Consulting, 2022, https://www.gwpc.org/wp-content/uploads/2021/09/2021_Produced_Water_Volumes.pdf). Efforts are underway to expand historic uses of produced water to offset freshwater needs in water-stressed regions, avoid induced seismic activity associated with its disposal, and extract commodities. Understanding the potential exposures from current and proposed produced water uses and management practices can help to inform health-protective practices. This review summarizes what is known about potential human exposure to produced water from onshore oil and gas development in the United States. We synthesize 236 publications to create a conceptual model of potential human exposure that illustrates the current state of scientific inquiry and knowledge. Exposure to produced water can occur following its release to the environment through spills or leaks during its handling and management. Exposure can also arise from authorized releases, including permitted discharges to surface water, crop irrigation, and road treatment. Knowledge gaps include understanding the variable composition and toxicity of produced water released to the environment, the performance of treatment methods, migration pathways through the environment that can result in human exposure, and the significance of the exposures for human and ecosystem health. Reducing these uncertainties may help in realizing the benefits of produced water use while simultaneously protecting human health.