Psychological flexibility is a model of human performance and well-being. It essentially entails an approach to life circumstances that includes openness, awareness, and engagement. It has roots in behavior analysis, and it is linked to a philosophy of science called functional contextualism and to a specific therapy approach called Acceptance and Commitment Therapy. One of the earliest and most developed research areas in which this model and therapy have been applied is chronic pain. This review describes psychological flexibility and its facets in more detail, sets them in a context of relevant psychological models, and examines related assessment and treatment methods. It also examines evidence, current challenges, and future directions. It is proposed that psychological flexibility, or an expanded model very much like it, could provide a basis for integrating current research and treatment approaches in chronic pain and health generally. This, in turn, could produce improved treatments for people with chronic pain and other conditions. Expected final online publication date for the , Volume 75 is January 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.