OBJECTIVES: In May 2013, the American Psychiatric Association released the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), a classification system for psychiatric conditions.  DSM-5 brings significant changes to many diagnostic categories as compared to the previous edition.  The objective of this review was to examine the changes in the Major Depressive Disorder (MDD) criteria and discuss the impact these changes may have for industry. METHODS: A line-by-line review of the DSM-5 and DSM-IV criteria for MDD was undertaken.  Significant changes were highlighted and discussed from the point of view of sponsors of clinical trials for psychopharmacologic agents being developed to treat MDD. RESULTS: The primary symptom criterion for MDD remains unchanged, requiring five of nine symptoms, over a two-week period.  The changes of note have to do with the differential diagnoses and specifiers.  One change that received significant attention in the time leading up to the publication of DSM-5 was the elimination of the bereavement exclusion, which discounted bereavement after the loss a loved one within the first two months as part of the normal grief process.  In terms of specifiers, a new addition in MDD is “with anxious distress,” referring to episodes of depression characterized by at least two of five symptoms of anxiety.  DSM-5 notes that this is associated with “greater likelihood of treatment nonresponse.”  Therefore, this is a factor sponsors may wish to consider in developing their trial inclusion/exclusion criteria. CONCLUSIONS: The significant changes in DSM-5 pose both challenges and opportunities for industry.  The changes in the DSM-5 criteria translate into changes for how we go about developing medical products to treat psychiatric disorders, including MDD.  There will need to be an investment in research and education, and sponsors must examine the possibility of developing new endpoints and outcome assessments for use in clinical trials.