Portal hypertension, one of the main complications of cirrhosis is a pathological increase of the portal pressure gradient and by the formation of portal-systemic collaterals that shunt part of the portal blood flow to the systemic circulation bypassing the liver. Non-selective beta-blockers (NSBBs) have been used for over 30 years for the primary and secondary prophylaxis of portal hypertension in patients with cirrhosis. NSBB decreases cardiac output via β1 receptors and causes splanchnic vasoconstriction through β2 receptors, leading to a reduction in portal inflow. They have proven efficacy in preventing first variceal bleeding and re-bleeding and in reducing mortality. The advantage of using NSBBs must be weighed against the risks associated with their chronic use. In addition recent data suggest about the limited use of NSBBs in a particular therapeutic window only. Outside this window it may cause deleterious effects. The beneficial window of NSBBs opened by the first appearance of esophageal varices at the risk of bleeding and would be closed by the development of refractory ascites or other severe complications like spontaneous bacterial peritonitis (SBP) / hepatic renal syndrome (HRS) the clinical hall mark of advanced liver diseases. The risk / benefit ratio of the non selective beta blocker therapy depends up on the stages of the cirrhosis, perhaps becoming unfavourable in patients with the most advanced stage. This article reviews the current evidence regarding the safety of non selective beta blockers in different Child Pugh classes of chronic liver disease for portal hypertension prophylaxis.