This report summarizes the best available evidence for a link between psychosocial factors and morbidity and mortality from cardiovascular diseases and cancer in the WHO European Region. The authors searched a total of 1822 Medline and PubMed articles published in English since January 2000, and identified 37 systematic reviews and meta-analyses. The psychosocial factors repeatedly identified as related to chronic diseases, in and outside work, included: high job demand, low autonomy, low control or high effort–reward imbalance, interpersonal conflicts, and low social support or low trust. The evidence suggests that multiple adverse psychosocial factors are independently associated with a range of chronic diseases throughout adulthood. In addition, the social gradient in health observed throughout adulthood may partly operate through psychosocial factors on the pathway between socioeconomic characteristics and health. Psychosocial factors might therefore become part of complex total risk-reducing interventions focusing on multiple risk factors.