To review systematically prospective, observational, cohort studies of the association between positive well-being and mortality using meta-analytic methods. Recent years have witnessed increased interest in the relationship between positive psychological well-being and physical health. We searched general bibliographic databases: Medline, PsycINFO, Web of Science, and PubMed up to January 2008. Two reviewers independently extracted data on study characteristics, quality, and estimates of associations. There were 35 studies (26 articles) investigating mortality in initially healthy populations and 35 studies (28 articles) of disease populations. The meta-analyses showed that positive psychological well-being was associated with reduced mortality in both the healthy population (combined hazard ratio (HR) = 0.82; 95% Confidence Interval (CI) = 0.76-0.89; p < .001) and the disease population (combined HR = 0.98; CI = 0.95-1.00; p = .030) studies. There were indications of publication bias in this literature, although the fail-safe numbers were 2444 and 1397 for healthy and disease population studies, respectively. Intriguingly, meta-analysis of studies that controlled for negative affect showed that the protective effects of positive psychological well-being were independent of negative affect. Both positive affect (e.g., emotional well-being, positive mood, joy, happiness, vigor, energy) and positive trait-like dispositions (e.g., life satisfaction, hopefulness, optimism, sense of humor) were associated with reduced mortality in healthy population studies. Positive psychological well-being was significantly associated with reduced cardiovascular mortality in healthy population studies, and with reduced death rates in patients with renal failure and with human immunodeficiency virus-infection. The current review suggests that positive psychological well-being has a favorable effect on survival in both healthy and diseased populations.