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Although the global prevalence of peptic ulcer disease (PUD) is decreasing, PUD is still one of the most common upper gastro-intestinal diseases in the world due to Helicobacter pylori infection and increased use of non-steroidal anti-inflammatory drugs. In Korea, the prevalence of H. pylori infection is also declining, but it is still the major cause of PUD. The outcomes of H. pylori infection are caused by imbalances between bacterial virulence factors, host factors, and environmental influences. In this review, we describe the prevalence trends of H. pylori infection in Korea, the mechanism of H. pylori infection-related PUD, and treatment strategies. (Korean J Gastroenterol 2016;67:289-299)