INTRODUCTION: With two thirds of cancer patients living for at least 5 years, clinical research has increasingly focused on the long-term health of cancer survivors. Contrary to the amount of knowledge on long-term consequences observations on late effects after childhood cancer in adult-onset cancer are sparse. Only limited literature is available recommending guidelines for long-term follow-up of cancer patients and their implementation in the delivery of health care. METHODS: In this review we summarize updated knowledge on the most frequent physical long-term effects after adult-onset cancer, and we discuss how these findings can be implemented in life-long follow-up programs of cancer survivors. RESULTS: Second cancer, cardiovascular disorders and gonadal dysfunction are the most common physical late effects along with fatigue. Common age-related co-morbidity reduces physical function in long-term cancer survivors. CONCLUSIONS: Cancer survivors have to be informed about their risk of late effects, and how to prevent them by life style adjustments and, if indicated, regular health care visits. Studies on late effects after cancer treatment should be combined with translational research in order to improve our understanding of pathophysiological mechanisms of long-term effects. The effectiveness of therapeutic interventions for reduction of these treatment sequelae in long-term survivors need to be investigated in randomized trials. Guidelines for life-long follow-up of cancer survivors should be established and will form the first step is the design of an individual life-long cancer survivor care plan.