Depression is a common condition in chronically ill immunosuppressed patients on long-term antifungal therapy with azoles. As both azoles and more recent antifungals are metabolised by the P450 enzymatic system in the liver, here we review the potential of clinically meaningful interactions between antidepressants and azoles. Selective serotonin reuptake inhibitors are safer compared to tricycle antidepressants when co-administered with azoles. More pharmacovigilance is needed.