Within the past ten years, an increasingly common and important collaboration has formed between behavioral biology and molecular genetics. By selectively disrupting the expression of a single gene, molecular biologists reason that the function of that targeted gene can be determined. In many cases, the phenotypic description of gene knock-out mice includes changes in behavior. Although this genetic technique offers new opportunities to study the mechanisms of behavior, in common with all behavioral techniques, there are some potential limitations that can compromise interpretation of studies of knock-out animals. The advantages and disadvantages of using knockout animals in behavioral studies will be discussed using examples from our studies of aggression.