Purpose: Classification is the cornerstone of clinical diagnostic practice and research. However, the extant psychiatric classification systems are not well supported by research evidence. In particular, extensive comorbidity among putatively distinct disorders flags an urgent need for fundamental changes in how we conceptualize psychopathology. Over the past decade, research has coalesced on an empirically based model that suggests many common mental disorders are structured according to two correlated latent dimensions: internalizing and externalizing. Methods: We review and discuss the development of a dimensional-spectrum model which organizes mental disorders in an empirically based manner. We also touch upon changes in the DSM-5 and put forward recommendations for future research endeavors. Results: Our review highlights substantial empirical support for the empirically based internalizing–externalizing model of psychopathology, which provides a parsimonious means of addressing comorbidity. Conclusions: As future research goals, we suggest that the field would benefit from: expanding the meta-structure of psychopathology to include additional disorders, development of empirically based thresholds, inclusion of a developmental perspective, and intertwining genomic and neuroscience dimensions with the empirical structure of psychopathology.