Substantial disagreement and uncertainty attend the question of whether the benefits from supplementing wild populations of anadromous salmonids with hatchery fish outweigh the risks. Prudent decisions about supplementation are most likely when the suite of potential benefits and hazards and the various sources of uncertainty are explicitly identified. Models help by indicating the potential consequences of various levels of supplementation but perhaps are most valuable for showing the limitations of available data and helping design studies and monitoring to provide critical data. Information and understanding about the issue are deficient. I discuss various benefits, hazards, and associated uncertainties for supplementation, and implications for the design of monitoring and research. Several studies to reduce uncertainty and facilitate prudent supplementation are described and range from short-term reductionistic studies that help define the issue or help avoid deleterious consequences from supplementation to long-term studies (ca. 10 or more fish generations) that evaluate the net result of positive and negative genetic, behavioral, and ecological effects from supplementation.