Human genetic studies have shown that single mutations in the Fkbp5 gene can have an influence on risk for depression, number of depressive episodes and response to antidepressant treatment (reviewed in Binder et al., 2009), clearly stressing the importance of Fkbp5 itself in these disorders and the need for further investigation, especially in the form of in vivo mammalian models. Here, FKBP5 is linked to major depressive disorder.