Heart transplantation remains the treatment of choice in selected patients with severe heart failure (HF) despite optimal medical therapy. Since long-term survival after HTX is improving, there is a growing need for evidence-based strategies that reduce long-term mortality resulting from both immunological and non-immunological risk. This manuscript summarizes recommendations for treatment of transplant vasculopathy, malignancy after transplantation, and prevention of corticosteroid induced bone disease. Based on actual understanding of cardiovascular risk factors in the population, preservation of renal function, prevention and treatment of hyperlipidemia and diabetes, as well as blood pressure control play an important role in the long-term follow-up after heart transplantation.