Experimental and clinical data pointing to antiviral and immunomodulatory effects of lithium have been reviewed in the context of new information accumulated in the last recent two decades, indicating a possible pathogenic role of viral infection and/or immune dysfunction in affective illness. Antiviral effects of lithium, particularly against herpes viruses, was demonstrated in both experimental and clinical conditions. Patients with affective illness taking lithium for prophylactic purposes have a greatly reduced frequency of labial herpes recurrences. The therapeutic action of oral and topical lithium administration on labial and genital herpes was also demonstrated in non-affective subjects. In both experimental conditions and in clinical studies with affective patients, lithium was shown to exert favorable effects on many parameters of cellular and humoral immunity. The evidence was also presented that lithium may alleviate the immune-endocrine component concomitant to an acute affective episode, such as acute phase reaction, cytokine secretion and hyperactivation of hypothalamic-pituitary-adrenal axis. It is speculated that the antiviral and immunomodulatory properties of lithium may contribute to psychotropic actions of this ionic drug, especially prevention of recurrences in affective illness.