Helicobacter pylori infection is highly prevalent worldwide and is a major cause of diseases occurring in the upper gastrointestinal tract. Successful eradication therapy improves H. pylori-related symptoms in functional dyspepsia, cures peptic ulcer disease and may prevent gastric cancer. During the past decade, the success rate of recommended eradication regimens declined from over 90% to about 80%, a critical threshold for effectiveness of the therapy according to the current guidelines. This is mainly because of the rising antimicrobial resistance and underlines that it is imperative to develop new treatment approaches. The prevention of the initial infection by a suitable vaccination might be the new therapeutic strategy for the future.