Considerable debate remains regarding the distinct biological activities of individual polyunsaturated fatty acids (PUFA). One of the most interesting yet controversial dietary approaches has been the possible prophylactic role of dietary gamma-linolenic acid (GLA) in treating various chronic disease states. This strategy is based on the ability of diet to modify cellular lipid composition and eicosanoid (cyclooxygenase and lipoxygenase) biosynthesis. Recent studies demonstrate that dietary GLA increases the content of its elongase product, dihomo-gamma-linolenic acid (DGLA), within cell membranes without concomitant changes in arachidonic acid (AA). Subsequently, upon stimulation, DGLA can be converted by inflammatory cells to 15-(S)-hydroxy-8,11,13-eicosatrienoic acid and prostaglandin E1. This is noteworthy because these compounds possess both anti-inflammatory and antiproliferative properties. Although an optimal feeding regimen to maximize the potential benefits of dietary GLA has not yet been determined, it is the purpose of this review to summarize the most recent research that has focused on objectively and reproducibly determining the mechanism(s) by which GLA may ameliorate health problems.