A systematic review was conducted to determine the extent to which an economic case has been made in high-income countries for investment in interventions to promote mental health and well-being. We focused on areas of interest to the DataPrev project: early years and parenting interventions, actions set in schools and workplaces and measures targeted at older people. Economic evaluations had to have some focus on promotion of mental health and well-being and/or primary prevention of poor mental health through health-related means. Studies preventing exacerbations in existing mental health problems were excluded, with the exception of support for parents with mental health problems, which might indirectly affect the mental health of their children. Overall 47 studies were identified. There was considerable variability in their quality, with a variety of outcome measures and different perspectives: societal, public purse, employer or health system used, making policy comparisons difficult. Caution must therefore be exercised in interpreting results, but the case for investment in parenting and health visitor-related programmes appears most strong, especially when impacts beyond the health sector are taken into account. In the workplace an economic return on investment in a number of comprehensive workplace health promotion programmes and stress management projects (largely in the USA) was reported, while group-based exercise and psychosocial interventions are of potential benefit to older people. Many gaps remain; a key first step would be to make more use of the existence evidence base on effectiveness and model mid- to long-term costs and benefits of action in different contexts and settings.