The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) includes numerous alterations to specific disorders, as well as fundamental conceptual and organizational changes. The purpose of this article is to review three fundamental conceptual changes in DSM-5: the harmonization of the manual with the International Statistical Classification of Diseases and Related Health Problems, the introduction of spectrum disorders and dimensional ratings, and the new organization of the manual. For each change, potential benefits and shortcomings are discussed in terms of innovation, limitations and clinical implications.