This meta-analysis aims to inform clinical practice of treatment strategies for adolescents with major depressive disorder (MDD). The efficacy of three empirically validated treatments was compared to determine the most effective treatment. These were: cognitive-behavioural therapy (CBT), selective serotonin reuptake inhibitor (SSRI) pharmacotherapy, and combination CBT and SSRI therapy. Inclusion criteria required studies to report a reliable and valid pre- and post-treatment measure and adequate data for Hedge's g effect size to be calculated. Forty-nine studies meeting the above inclusion criteria were found and included in the analysis. Although all three treatment strategies were found to be effective, analysis revealed no significant difference in treatment outcome among CBT, SSRI, and combination therapy. An investigation of moderator variables revealed months to follow-up to significantly influence the relationship between treatment type and treatment outcome. Given that CBT has no side effects, is more cost effective, and is equally as effective as SSRI therapy and combination therapy, the current study makes a strong case for CBT as a first-line treatment strategy for adolescents with MDD.