OBJECTIVES: To conduct a systematic review of literature in on epidemiology and economic studies for patients diagnosed with Non-Psychotic Major Depressive Disorder (MDD). METHODS: The initial search strategy was developed in the PubMed/Medline database, and was then translated for the Cochrane and Embase database searches. Search strings for epidemiology and economics studies for MDD were constructed using varied approaches that included the use of MeSH terms, as well as keywords that would afford the best retrieval. Search statements were then combined to produce a final search set. Additional parameters were placed on the final search strategy to limit the retrieval to articles written in English, involving human subjects and published between 2000 and 2010.  RESULTS: Our search revealed 289 articles for epidemiology and 200 articles for economic studies on MDD from PubMed/Medline/Embase/Cochrane databases. After removing duplicates and non-relevant articles, 17 for epidemiology and 26 for economic studies were included in the final analysis. Fifteen studies on epidemiology were focused on MDD prevalence, one study was on cumulative incidence. Prevalence estimates were higher for lifetime than past year and ranged between 3.1% and 26.6% for lifetime prevalence and between 1.5% and 11.7% for past-year prevalence. Two studies examined burden of illness, one study budgetary impact of MDD, 14 studies examined cost effectiveness of MDD treatments, 3 studies examined cost utility analysis and 6 other studies examined retrospective claims analysis.  CONCLUSIONS: MDD prevalence was higher in the lifetime estimates, when compared to the estimates reflecting shorter time frames, although there appeared to be greater variability in the lifetime estimates. Overall, the cost of treating MDD varied with type of study, study time frame, study perspective, the year in which the costs were calculated, and the pharmacotherapy prescribed.