Most peptic ulcers are caused by Helicobacter pylori infection. The infection is best diagnosed by a radiolabeled carbon urea breath test, which also can prove that eradication therapy was successful. Serologic testing is useful for establishing prior or present infection but not to determine if the infection has been eradicated. Endoscopic tests usually are not needed to establish a diagnosis. Modern ulcer treatment consists of H. pylori eradication in infected patients. A combination of a proton pump inhibitor plus clarithromycin and amoxicillin or a proton pump inhibitor plus bismuth, metronidazole, and tetracycline are the most effective regimens. Reinfection is less than 2% per year in developed countries. Evidence suggests that H. pylori eradication may foster the development of erosive esophagitis, but confirmatory studies are needed. Studies also suggest an interaction between H. pylori infection and peptic ulcers related to the use of nonsteroidal antiinflammatory drugs (NSAIDs). However, the studies are conflicting: One shows that H. pylori eradication protects against NSAID-related ulcers; another suggests protection afforded by the infection. Non-H. pylori peptic ulcers remain a challenge, especially in the United States, where one study showed that 42% of peptic ulcers were not due to the infection. Some non-H. pylori ulcers are refractory to usual doses of antisecretory drugs.