Improvements in overall survival early after liver transplantation result in a growing number of patients with the potential for long-term survival. Data available on long-term survival, to date, reflect the situation of patients who received their liver transplant during a very different health-care era. Translating these data into the current medical era of liver transplantation is an important task, as a better understanding of aspects associated with morbidity and mortality is fundamental in improving the long-term outcome of liver transplant recipients. Malignancy screening, optimal treatment of recurrent disease and adequate management of metabolic disease are crucial contributions to advance patient care. In this Review, data specific to the liver transplant recipient will be evaluated and, in the absence of sufficient evidence at this time, recommendations and guidelines for the general population on management of long-term concerns will be assessed for their applicability after liver transplantation. In addition, other preventive strategies relating to pregnancy, contraception and vaccination are reviewed in detail.