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Selective serotonin reuptake inhibitors (SSRIs) are one of the most frequently prescribed drugs for the treatment of depression in children and adolescents. Skin can produce serotonin and transform it into melatonin. Pathways for the biosynthesis of serotonin and melatonin have been characterized in human and rodent skin and in their major cellular populations. Serotonin is known to have several roles in skin—e.g., pro-edema, vasodilatory, proinşammatory, and pruritogenic. Cutaneous adverse effects of SSRIs are seldomly seen and include mild photosensitivity, pruritus, urticaria, toxic epidermal necrolysis, Steven-Johnson syndrome, and leukocytoclastic vasculitis (2,3). SSRI induced skin reactions are dose independent. In this article, we aimed to report a case of an adverse drug reaction to sertraline in a child with Major Depression. A 15-year-old male attended to Child and Adolescent Psychiatry Outpatient Clinics of Marmara University Medical School with insomnia, anhedonia, loss of appetite, and concentration difficulties. The patient was diagnosed with Major Depression. The patient did not have any past medical or family history of allergy or dermatological diseases. Antidepressive treatment with sertraline 25 mg daily was initiated. After three days of treatment maculopapular, erythematous itching rash especially on sun-exposed areas suddenly appeared. The rash was over the forearm, wrist, elbow and hand, together with some facial involvement. There was no palm or sole involvement noted. An adverse drug reaction (ADR) induced by sertraline was suspected and drug treatment was discontinued. This skin reaction was consulted to the dermatologist. Topical steroid treatment was initiated. Ten days later, the symptoms decreased. A new antidepressant drug is planned following the dermatological treatment. Receptors for serotonin and melatonin receptors are expressed in keratinocytes, melanocytes, and fibroblasts and these mediate phenotypic actions on cellular proliferation and differentiation. Melatonin exerts receptor-independent effects, including activation of pathways protective of oxidative stress and the modification of cellular metabolism. The cutaneous serotoninergic/melatoninergic system could counteract or buffer external (environmental) or internal stresses to preserve the biological integrity of the organ and to maintain its homeostasis.