Patient and liver graft survival rates have improved significantly in the last decades, leading to complications mainly related to long-term immunosuppression. Prevention of, screening for metabolic syndrome, cardiovascular disease, de novo diabetes mellitus, renal dysfunction, and malignancies and their management are mandatory due to important causes of morbidity and mortality in this patient population. Quality of life (QoL) and functional benefits are clearly better compared to preoperative status; however, post-liver transplantation (LT) complications may impair and alter QoL scores. Individualized immunosuppression managed by transplant physicians and collaboration with other non-transplant specialists for recognition and treatment of medical complications and comorbidities after LT is the key to enhanced QoL and life expectancy of this patient population.