There continues to be a lack of evidence-based programs in the primary prevention of chronic diseases. This also applies to overweight and obesity, a health problem for which primary prevention in childhood is seen as key. Primary prevention is characterized by its focus on specific risk factors of a disease. For the development of effective prevention programs, a theoretical model of health and health behavior changes is an important prerequisite. With regard to such models, an epidemiologic life course approach may offer new perspectives for primary prevention. Major prevention concepts are those considering population versus selective, high-risk group strategies and prevention approaches targeting behavior or environmental and social conditions. All modern prevention programs require a systematic evaluation that should not only focus on processes, but also on health outcomes. Lack of resources or short program time spans are frequently cited as obstacles for stringent program evaluation. These barriers and others need to be tackled to further develop evidence-based primary prevention.