The proton pump inhibitors (PPIs) omeprazole, lansoprazole, and pantoprazole are widely used as antisecretory drugs and, in association with antibiotics, for the treatment of Helicobacter pylori infections. PPIs possess antibacterial activity against H. pylori in vitro, and may also exert an anti-inflammatory effect by interfering with the cellular immune response to infection. Their antimicrobial activity is selective for H. pylori. Lansoprazole is the most effective, although its bactericidal activity is similar to that of omeprazole. Pantoprazole is the least effective. The mechanisms that account for the antibacterial effects of PPIs may depend on a structural similarity of PPIs to antibiotics which are active against H. pylori, on the inhibition of bacterial urease exerted by PPIs, or on the possible interaction of PPIs with bacterial ATPases that regulate the transmembrane ion flux. Recent studies have shown that PPIs have anti-inflammatory actions and can interfere with the host-bacteria interactions. Lansoprazole can bind to polymorphonuclear leukocytes that infiltrate the gastric mucosa colonized by H. pylori and can thus inhibit the oxidative burst of activated inflammatory cells. In an in vivo study, lansoprazole reduced the degree of activity of histologic gastritis independently of the presence of H. pylori. In another study, omeprazole was capable of inhibiting the cytotoxic activity of NK T cells. Investigation of PPI interactions with H. pylori activities and the cellular immune response to the infection may help us to understand the pathogenic mechanisms of H. pylori-associated diseases and enable clinicians to better treat them.