Acceptance and commitment therapy (ACT) is a set of evidence-based principles designed to reduce human suffering and promote well-being via instantiating psychological flexibility. Situated within the broad family of cognitive-behavioral therapies, ACT conceptualizes psychopathology in terms of 6 inter-related psychological inflexibility processes. ACT is supported by a substantial body of research and recognized as an evidence-based intervention by numerous government and health care organizations. Due to its process-based nature, ACT has been adapted across a range of diverse areas. In this article, we provide an overview of ACT across conceptual, clinical, and research domains, and introduce this special issue.