There continues to be debate about the influence of personality disorder on the outcome of depressive disorders and is relative interactions with treatment. To determine whether personality disorder, both generically and in terms of individual clusters, leads to a worse outcome in patients with depressive disorders and whether this is influenced by type of treatment, a systematic electronic search of MEDLINE, CINAHL, and PsycINFO from 1966, 1982, and 1882, respectively, until February 2007 was undertaken. The keyword terms depression, mental illness, and personality disorder were used. All references were reviewed and personal correspondence was undertaken. Only English language papers were considered. Any English language paper studying a depressed adult population was considered for inclusion. Studies needed to clearly define depression and personality disorder using peer-reviewed instruments or International Classification of Disease/Diagnostic Statistical Manual criteria. Outcome assessment at greater than 3 weeks was necessary. Final inclusion papers were agreed on by consensus by at least two reviewers. All data were extracted using predetermined criteria for depression by at least two reviewers in parallel. Disagreement was settled by consensus. Complex data extraction was confirmed within the study group. Data were synthesized using log odds ratios in the Cochrane RevMan 5 program. The finding of comorbid personality disorder and depression was associated with a more than double the odds of a poor outcome for depression compared with those with no personality disorder (OR 2.16, CI 1.83-2.56). This effect was not ameliorated by the treatment modality used for the depressive disorder. This finding led to the conclusion that personality disorder has a negative impact on the outcome of depression. This finding is important in considering prognosis in depressive disorders.