Epistasis, the interaction between genes, is a topic of current interest in molecular and quantitative genetics. A large amount of research has been devoted to the detection and investigation of epistatic interactions. However, there has been much confusion in the literature over definitions and interpretations of epistasis. In this review, we provide a historical background to the study of epistatic interaction effects and point out the differences between a number of commonly used definitions of epistasis. A brief survey of some methods for detecting epistasis in humans is given. We note that the degree to which statistical tests of epistasis can elucidate underlying biological interactions may be more limited than previously assumed.