In children and adolescents, antidepressants are used in the treatment of depressive symptoms and several other psychiatric conditions. In the treatment of mild and moderate depressive symptoms, non-pharmacological approaches such as psychotherapy play a major role, a severe symptomatology may demand a combination with antidepressants. As first-choice medication for the treatment of juvenile depression, the selective serotonin reuptake inhibitor (SSRI) fluoxetine is recommended, due to its efficacy and approval. As second-choice antidepressants the SSRIs sertraline, escitalopram and citalopram might be used. Other antidepressants - such as tricyclic antidepressants, α(2)-adrenoceptor antagonists, selective noradrenalin reuptake inhibitors (SNRI) - may be alternatively used, but not as first- or second-choice medications. In the case of "off-label" use, patients and parents have to be carefully informed prior to the start of medication, after a thorough risk-benefit analysis. In the following overview we address a general framework, therapeutic strategies and the issues of antidepressant pharmacotherapy for the treatment of unipolar depression in childhood and adolescence.