This chapter reviews the methods for validating animal models of psychiatric disorders and discusses specific models of anxiety in mice. It demonstrates the importance of understanding the validity of a particular animal model, which assists in determining its clinical relevance in the context of careful interpretation. Currently, two main types of genetically modified mice are used in laboratory: knockout mice or knock-in mice and transgenic mice. The chapter reviews how state-of-the-art transgenic technology can be used to make animal models that allow us to consider the contribution of particular genes to anxiety-like behaviors. Several lines of evidence from human studies have implicated the 5-HT1A receptor in affective disorders. The studies of the 5-HT1A receptor provide an illustrative example of the strengths and weaknesses inherent in using the genetic technologies to investigate the pathophysiology of anxiety.