This chapter provides an overview of the different physiological markers frequently linked to Positive Affect (PA) with a focus on those most likely responsible for the growing body of literature connecting PA to better health. In particular, we focus on the cardiovascular, endocrine, and immune systems. These three systems are interconnected and support physiological responses to emotions, as well as major bodily functions that are needed for life adaptation (e.g., stress response), survival, and health-related processes. Evidence of the links between PA and physiology are reviewed in the context of theoretical frameworks that have been developed in the past three decades. Throughout the review we also pay attention to key methodological issues present in research on physiological function, ending with future directions that can help accelerate the field of positive health psychology and positively impact human well-being.