The epidemiology of peptic ulcer disease (PUD) has undergone significant changes since the discovery of Helicobacter pylori. Various aetiologies contribute to recurrent PUD. Ulcers related to untreated H. pylori infection tend to recur. Use of NSAIDs, low-dose aspirin and dual anti-platelet therapy have become important risk factors for recurrent ulcers and their complications as the proportion of H. pylori-related ulcers declines. Recent data have shown that H. pylori-negative, NSAID-negative idiopathic peptic ulcers are on the rise and carry a higher risk of recurrent ulcer bleeding and mortality. Effective management of recurrent PUD relies on identification and modification of treatable risk factors. Persistent H. pylori infection should be carefully ruled out. Choice of an effective H. pylori eradication regimen should be based on local antibacterial resistance patterns. For patients who need long-term NSAID therapy, the initial choice of an NSAID relates to a patient's cardiovascular risk, and the need for therapy to decrease gastrointestinal (GI) complications is determined by the severity and number of GI risk factors. For patients on dual anti-platelet therapy, strategies to prevent recurrent ulcer disease and its complications centre on balancing the bleeding and thrombotic risks of individual patients. Long-term proton pump inhibitor maintenance therapy may be necessary to prevent recurrent ulcer bleeding for patients with ulcer bleeding from H. pylori-negative, NSAID-negative ulcers, and for patients who require NSAID or aspirin maintenance therapy.