This article presents a framework for art therapy practice and research called Adaptive Response Theory (ART), founded on constructs from evolutionary biology and human development. The theory is based on human responses to threats to well-being (bio-physiological and psycho-social-spiritual), as well as, how art making and imaginative processes align with the current conceptualization of the brain as a predictive machine. Based on four components of art therapy practice (art, art making, patient/client, and therapist), the framework delineates how mechanisms of change can be tracked systematically to determine the outcomes of interventions.