Increasing evidence indicates that psychological factors important to therapy effectiveness are associated with physiological activity. Knowledge of the physiological correlates of therapy process variables has the potential to provide unique insights into how and why therapy works, but little is currently known about the physiological underpinnings of specific therapy processes that facilitate client growth and change. The goal of this article is to introduce therapy process researchers to the use of physiological methods for studying therapy process variables. We do this by (a) presenting a conceptual framework for the study of therapy process variables, (b) providing an introductory overview of physiological systems with particular promise for the study of therapy process variables, (c) introducing the primary methods and methodological decisions involved in physiological research, and (d) demonstrating these principles and methods in a case of therapeutic presence during couple therapy. We close with a discussion of the promise and challenges in the study of physiological correlates of therapy process variables and consideration of future challenges and open questions in this line of research. Online supplemental materials include additional resources for therapy process researchers interested in getting started with physiological research. (PsycInfo Database Record (c) 2020 APA, all rights reserved).