BACKGROUND Depression may affect 2% to 8% of children and adolescents, with a peak incidence around puberty. It may be self-limiting, but about 40% of affected children experience a recurrent attack, one third of affected children will make a suicide attempt, and 3% to 4% will die from suicide. METHODS We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of pharmacological, psychological, combination, and complementary treatments for depression in children and adolescents? What are the effects of treatments for refractory depression in children and adolescents? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS We found 21 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS In this systematic review we present information relating to the effectiveness and safety of the following interventions: citalopram, cognitive behavioural therapy (CBT) (individual or group, to prevent relapse), electroconvulsive therapy, escitalopram, family therapy, fluoxetine (alone or with cognitive therapy or CBT), fluvoxamine, group therapeutic support (other than CBT), guided self-help, individual psychodynamic psychotherapy, interpersonal therapy, lithium, mirtazapine, monoamine oxidase inhibitors (MAOIs), omega-3 polyunsaturated fatty acids, paroxetine, sertraline (alone or with CBT), St John's Wort (Hypericum perforatum), tricyclic antidepressants, and venlafaxine.