Non-alcoholic fatty liver disease (NAFLD), specifically its progressive form non-alcoholic steatohepatitis (NASH), represents the fastest growing indication for liver transplantation in Western countries. Diabetes mellitus, morbid obesity and cardiovascular disease are frequently present in patients with NAFLD who are candidates for liver transplantation. These factors require specific evaluation, including a detailed pre-surgical risk stratification, in order to improve outcomes after liver transplantation. Moreover, in the post-transplantation setting, the incidence of cardiovascular events and metabolic complications can be amplified by immunosuppressive therapy, which is a well-known driver of metabolic alterations. Indeed, patients with NASH are more prone to developing early post-transplant complications and, in the long-term, malignancy and cardiovascular events, corresponding to higher mortality rates. Therefore, a tailored multidisciplinary approach is required for these patients, both before and after liver transplantation. Appropriate candidate selection, lifestyle modifications and specific assessment in the pre-transplant setting, as well as pharmacological strategies, adjustment of immunosuppression and a healthy lifestyle in the post-transplant setting, play a key role in correct management.