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Liver transplantation (LT) is a cost-effective therapy for advanced liver disease. Although LT significantly improves long-term survival, it requires strict control of immunosuppressants and their potential complications. Several available immunosuppressive drugs include glucocorticoids, calcineurin inhibitors, mycophenolate, mTOR inhibitors, and anti-CD25 antibodies. These drugs act particularly in T lymphocytes, depleting them, deviating their traffic, or blocking their response pathways. The main complications after LT include renal failure and infectious, immunological, biliary, vascular adverse events, metabolic, cardiovascular, and neoplastic diseases, especially during the first months. Bacteria, viruses, and fungi can cause infections in these patients. Prophylaxis against Herpes simplex virus, Varicella zoster virus, Cytomegalovirus, Pneumocystis jirovecii, Candida spp., and Aspergillus spp. should be considered according to the presence of risk factors. Among immunological complications, acute cellular rejection is common (30% of LT) but usually responds to immunosuppressive escalation. Also, chronic rejection appears in 3-17% of LT, but only half of the recipients respond to increased immunosuppressants. Appropriate treatment of the underlying etiology is essential, especially in autoimmune diseases, hepatitis B and C virus infection. Lifestyle changes must be encouraged in all patients, and alcohol consumption avoided (especially in alcohol use disorder). Due to the increased risk of cancer, neoplasms must be actively monitored, as well as osteoporosis and other metabolic disorders such as diabetes and cardiovascular disease.