Suicidal behaviour is an important public health problem globally and in Africa. A brief overview of the nature and severity of the problem is provided, but the primary aim of this paper is to identify priorities and prevention strategies for reducing suicidal behaviour in South Africa by discussing a framework for a proposed national prevention programme. South African suicide rates range from 11.5 per 100 000 to as high as 25 per 100 000 of the population, depending on sampling procedures and research methods. About 11% of all non-natural deaths are suicide related. On average 9.5% of non-natural deaths in young people are due to suicide. It is a complex phenomenon and risk factors are, therefore, multifactorial and multidimensional. Some of the most important ones are identified and several priorities and prevention possibilities for reducing suicidal behaviour are recommended. The outline and structure for such a national suicide prevention programme is underpinned by research undertaken locally and internationally. It requires a comprehensive multi-sectoral approach that involves both health care and non-health care sectors and action at various levels utilising a framework based on a set of guiding principles and a range of strategies with specific objectives as a national priority within an interdisciplinary context.