Laughter is a very common behaviour in everyday life, nevertheless scientific literature is lacking in studies which examine closely its nature. The study aims are: to summarise the present knowledge about laughter and its relation with depression and to make hypotheses on its possible therapeutic function. In the first part of the review the main data existing about encephalic structures involved in laughter genesis, which show participation of cortical and subcortical regions, are reported and the effects of laughter on the organism physiologic equilibrium, particularly on the neuroendocrine and immune systems, are described. In the second part, scientific evidence about the influence of depression on the ability to laugh are referred, which suggests that reduction of laughter frequency is a symptom of the disease and that its increase may be used as a marker of clinical improvement. Finally, the main assumptions supporting the hypothesis of the therapeutic action of laughter on depression are examined: first of all, it has been demonstrated that laughter is able to improve mood directly and to moderate negative consequences of stressful events on psychological well-being; in addition, it is possible that the stimulation of particular cerebral regions, involved in depression pathogenesis, and the normalisation of the hypothalamic pituitary adrenocortical system dysfunctions, both mediated by laughter, can counteract efficiently depressive symptoms; finally, the favourable effects of laughter on social relationships and physical health may have a role in influencing the ability of depressed patients to face the disease.