Understanding of the genetic influences on obesity has increased at a tremendous rate in recent years. By some estimates, 40 to 70 percent of the variation in obesity-related phenotypes in humans is heritable. Although several single-gene mutations have been shown to cause obesity in animal models, the situation in humans is considerably more complex. The most common forms of human obesity arise from the interactions of multiple genes, environmental factors, and behavior, and this complex etiology makes the search for obesity genes especially challenging. This article discusses the strategies currently being used to search for human obesity genes and recent promising results from these efforts.