Depression is becoming an increasingly significant challenge for public and societal health, affecting both adults and children and adolescents worldwide. Diagnosis is based on identifying five characteristic symptoms persisting for at least two weeks. Diagnosing children may be more challenging due to the masking of symptoms in behavioral patterns. Treatment mainly involves medications such as selective serotonin reuptake inhibitors (SSRIs), but due to limited availability of approved drugs, off-label use is often resorted to. Fluoxetine is an important drug in the treatment of depression in children, showing efficacy and good tolerability. However, patients should be monitored for suicidal thoughts. Sertraline, although not registered for the treatment of depression in children, is often used off-label and shows a positive response to treatment. Escitalopram, approved for the treatment of depression in children over 12 years of age, is stronger and more selective than citalopram, but its approval is based on limited clinical trials. Children and adolescents have different pharmacokinetic and pharmacodynamic profiles, requiring a personalized approach to therapy. Therapy monitored by drug concentration in the blood (TDM) is an important tool for adjusting the dose to the patient's needs. The role of pharmacists in monitoring antidepressant therapy in children and adolescents is valuable and can contribute to improved clinical outcomes. The article analyzes the efficacy and safety of antidepressant drugs in children and adolescents, with an emphasis on SSRIs, and identifies issues related to therapy selection, with particular emphasis on personalized care and the growing role of TDM in optimizing treatment outcomes.