Approximately 90% of liver transplant patients are alive after 1 year and 75% after 5 years with the majority leading full and near-normal lives. However, although early mortality rates after transplantation have fallen dramatically over the last 2 decades, the rates of late graft loss and patient death have remained constant. Thus, understanding of the causes of graft and patient failure is essential to improve long-term outcomes. In the early days after liver transplantation, ischemia and reperfusion injuries predominate, with acute cellular rejection relatively common in first 3 months. Thereafter, the causes of graft dysfunction are variable with disease recurrence as a major cause of graft loss. In this review, we discuss causes of graft dysfunction after 6 months.