Transjugular intrahepatic portosystemic shunt (TIPS) is used to treat complications of cirrhosis such as variceal bleeding and refractory ascites, but it also bears the risk of liver failure, overt hepatic encephalopathy (HE) and cardiac decompensation. Variceal bleeding may be controlled using endoscopic and medical treatment in patients with compensated cirrhosis; in decompensated patients, however, TIPS improves survival. Therefore, an early TIPS (within 72h or if later, still early after bleeding) might improve the survival of patients by preventing an inflammatory response and bacterial translocation. Both these processes mediate an impaired immunological and hemodynamic response, thereby facilitating the development of acute-on-chronic liver failure (ACLF) and/or death. Similarly, in patients with refractory ascites, TIPS should be used early in treatment to prevent acute kidney injury (AKI) and hepatorenal syndrome (HRS) after precipitating events induced by complications of portal hypertension. Whether TIPS and/or embolization should be used to treat portal vein thrombosis and spontaneous shunts is still a matter of debate and should be further investigated. In summary, the careful selection of patients for TIPS is crucial. New biomarkers, especially those evaluating systemic inflammation and bacterial translocation, might improve the predictive value of established clinical parameters such as bilirubin and overt HE. However, a significant amount of further research must be carried out.