Cirrhosis is mostly caused by a chronic wound healing reaction following sustained hepatocellular injury that leads to liver fibrosis, nodular regeneration, and vascular architectural remodeling. Portal hypertension (PH) represents the key clinical outcome since cirrhosis-related complications depend on its progression and severity. Advanced stages are characterized by major alterations of systemic hemodynamics and metabolic derangements leading to liver and multiorgan failure. Systemic inflammation and an inappropriate immune response represent the key physiopathological background supporting rapid and sometimes unpredictable acute deterioration of liver function known as acute-on-chronic liver failure (ACLF).