The pharmacological treatment of mood and anxiety disorders has for long relied on the serendipitous findings of monoaminergic and benzodiazepine drugs more than 50 years ago. These treatments, however, are therapeutically insufficient and even though more recently developed drugs are particularly improving side effects, the efficacy or response rate of the drugs has fundamentally not improved. Therefore it is necessary to develop new methods to identify novel mechanisms not based on merely the symptomatology, but on biologically relevant (endo) phenotypes. This review examines the option of integrating mouse and human behavioural genetics to aid the identification of the putative underlying pathophysiological mechanisms and pharmacological targets for psychiatric disorders.