Significant upper gastrointestinal bleeding resulting from stress ulceration is a serious life-threatening complication. However, it occurs relatively rarely even in the sickest patients. Therefore, guidelines suggest that prophylaxis (e.g., with acid-suppressive therapy) should be reserved for highly selected patients. Despite these recommendations, numerous studies suggest that many hospitalized patients are inappropriately placed on acid-suppressive therapy (AST) for the sole purpose of preventing stress ulceration. Moreover, it appears that once AST is started, medications are continued even after discharge, resulting in further unnecessary expenditure of resources. National and local efforts are needed to curtail this practice that places patients at risk for drug side effects while affording them little or no benefit.