The Hierarchical Taxonomy of Psychopathology (HiTOP) is a dimensional framework for psychopathology advanced by a consortium of nosologists. In the HiTOP system, psychopathology is grouped hierarchically from super-spectra, spectra, and subfactors at the upper levels to homogeneous symptom components and maladaptive traits and their constituent symptoms, and maladaptive behaviors at the lower levels. HiTOP has the potential to improve clinical outcomes by planning treatment based on symptom severity rather than heterogeneous diagnoses, targeting treatment across different levels of the hierarchy, and assessing distress and impairment separately from the observed symptom profile. Assessments can be performed according to this framework with the recently developed HiTOP-Self-Report (HiTOP-SR). Examples of how to use HiTOP in clinical practice are provided for the internalizing spectrum, including the use of the Unified Protocol and other modularized treatments, measurement-based care, psychopharmacology, and in traditionally underserved populations. Future directions are discussed including HiTOP’s use in further developing transdiagnostic treatments, extending the model to include other information such as environmental factors, establishing the treatment utility of clinical assessment for the HiTOP-SR, developing new treatments, and disseminating the model.