There is accumulating evidence that positive affect may protect against ill-health and risk of disease. Here, we summarize results from our research program into the biological correlates of positive affect. Data have been collected from middle-aged men and women, with positive affect assessed through repeated ratings of happiness over a working day. The results indicate that greater happiness is associated with lower salivary cortisol both on working and nonworking days, reduced fibrinogen stress responses, and lower ambulatory heart rate in men. These effects are independent of age, socioeconomic status, smoking, body mass and psychological distress. A 3 year follow-up has confirmed these biological associations with happiness. In addition, we found that happiness was inversely related to ambulatory systolic blood pressure on follow-up, again independently of potential confounders including negative affect. These results suggest that positive affective states are linked to favorable health outcomes through their influence on health-related biology, and may be particularly relevant in old age, when the accumulation of risk factors leads to increased risk of chronic disease.