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 and certain neurologic conditions.  DSM-5 brings significant changes to many diagnostic categories as compared to the previous DSM-IV-TR.  The objective of this review was to examine the changes in the Schizophrenia 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 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 Schizophrenia. RESULTS: The primary diagnostic criteria for Schizophrenia in DSM-5 are little changed.  The major change in the so-called “active-phase symptoms” is with the mix of symptoms that can meet this criterion.  Five key symptom areas must be present to meet criteria.  In DSM-IV, any two symptoms were sufficient and in some limited cases, even just one was enough (bizarre delusions or Schneiderian first-rank auditory hallucinations – conversing voices).  According to the DSM-5 criteria, there always must be at least two symptoms to meet Criterion A, and one of the two must be either delusions, hallucinations, or disorganized speech.  Other important changes include changes to the course specifiers, the elimination of Schizophrenia subtypes, and the addition of an optional framework for clinicians to rate the severity of the primary symptoms. CONCLUSIONS: The changes in DSM-5 pose both challenges and opportunities for industry.  The changes in the DSM-5 criteria may translate into changes for how we go about developing medical products to treat psychiatric disorders, including Schizophrenia.  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.