Systemic complications often occur in patients with advanced liver disease. In particular, the development of renal complications (acute kidney injury, hepatorenal syndrome), acute-on-chronic liver failure, cardiopulmonary diseases, or relative adrenal insufficiency can be serious in patients with advanced liver disease and may determine the patient’s quality of life and prognosis. Therefore, the early diagnosis of possible complications is the key to the prompt initiation of specific treatments that can improve quality of life and survival. For this purpose, networking with reference centers where multidisciplinary units are available is essential so that every patient is evaluated in clinical discussions involving specialists from different fields.