The working relationship between patient and therapist is a core aspect of psychotherapy. In this chapter, the authors consider how the therapeutic relationship may be explained by the basic social-psychological mechanism of interpersonal synchrony, defined as the temporal coordination of patient’s and therapist’s mutual behavioral, physiological, and neurological functions. Part 1 reviews clinical-psychological research on psychotherapy. Part 2 discusses social-psychological research on interpersonal synchrony and its relevance to the therapeutic relationship. Part 3 integrates the clinical- and social-psychological literatures in the INterpersonal SYNChrony (IN-SYNC) model of psychotherapy (Koole & Tschacher, 2016). Part 4 reviews empirical research on the IN-SYNC model. Part 5 summarizes the authors’ main conclusions and considers the broader implications of this work. The authors conclude that interpersonal synchrony has much promise as a basic social-psychology mechanism that may help us to understand how psychotherapy works.