Selective seritonin reuptake inhibitors (SSRIs) are widely used antidepressants that are often safer than alternatives, but may produce a variety of cutaneous reactions including spontaneous bruising, pruritus, urticaria, angioedema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema nodosum, alopecia, hypertrichosis, leukocytoclastic vasculitis, and an acneiform eruption. We review this category of medications and its side effects. Many cutaneous alterations seen in association with SSRIs can be serious, some even life threatening. Because there appears to be cross-reactions between SSRIs, even though they have different chemical structures, it is advisable to use another family of antidepressants if an SSRI is linked with a serious skin eruption.