Early detection of bleeding site by immediate endoscopy is the key of effective treatment in massive upper gastrointestinal (GI) bleeding. Upper GI endoscopy gives useful information about the risk, re-bleeding and mortality. Algorithm of treatment is also based on findings upon early endoscopy. Meta-analysis of prospective, randomized, multicenter clinical trials assessing H2-receptor antagonists and proton pump-inhibitors in the treatment of peptic ulcers suggest that these drugs cannot be justified for stopping bleeding or prevent re-bleeding. Other drugs, such as somatostatin, might be effective, but further studies are needed to prove their effectiveness. Both vasopressin and somatostatin are also successfully employed the treatment of bleeding related to portal hypertension, and a recent meta-analysis found significant benefit for beta-blockade in the prevention of recurrent bleeding. Although beta-blocker therapy does not improve survival, it reduces re-bleeding rate, therefore, it can be used as prophylactic therapy for esophageal varices. As for the treatment of erosions, none of the drugs currently employed are effective in reducing or preventing clinically significant bleeding.