Rationale The 5-HT 7 receptor is a more recently discovered G-protein-coupled receptor for serotonin. The functions and possible clinical relevance of this receptor are not yet fully understood. Objective The present paper reviews to what extent the use of animal models of human psychiatric and neurological disorders have implicated the 5-HT 7 receptor in such disorders. The studies have used a combination of pharmacological and genetic tools targeting the receptor to evaluate effects on behavior. Results Models of anxiety and schizophrenia have yielded mixed results with no clear role for the 5-HT 7 receptor described in these disorders. Some data are available for epilepsy, migraine, and pain but it is still very early to draw any definitive conclusions. There is a considerable amount of evidence supporting a role for the 5-HT 7 receptor in depression. Both blockade and inactivation of the receptor have resulted in an antidepressant-like profile in models of depression. Supporting evidence has also been obtained in sleep studies. Especially interesting are the augmented effects achieved by combining antidepressants and 5-HT 7 receptor antagonists. The antidepressant effect of amisulpride has been shown to most likely be mediated by the 5-HT 7 receptor. Conclusions The use of pharmacological and genetic tools in preclinical animal models strongly supports a role for the 5-HT 7 receptor in depression. Indirect evidence exists showing that 5-HT 7 receptor antagonism is clinically useful in the treatment of depression. Available data also indicate a possible involvement of the 5-HT 7 receptor in anxiety, epilepsy, pain, and schizophrenia.