Helicobacter pylori causes persistent infection and inflammation in the human stomach, yet only a small fraction of infected people develop illness. An important question is why this diversity exists in infection outcome. In recent years, there has been evidence of substantial phenotypic as well as genotypic diversity of H. pylori. Three different phenotypes--production of vacuolating cytotoxin, presence of cagA, and ability for strong PMN activation--appear to be linked to one another and to the propensity for a H. pylori strain to cause peptic ulcer disease. Further investigation in this field may help to define which infected people bear the highest risk for serious clinical consequences, and ultimately to define optimal vaccine candidates and strategies.