Nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids are very commonly prescribed. Morbidity and mortality from nonsteroidal anti-inflammatory drugs (NSAID) and steroids continue to be a significant health problem. In this paper are reported: 1) the biological insights into injurious effects of NSAIDs and steroids on mucosal protection and repair; 2) our clinical experience in the diagnosis and the management of children affected by secondary ulcer disease induced by therapeutic doses of NSAIDs and steroids; 3) the guidelines in the prevention of the NSAIDs and steroids-induced gastric damage.