Here we review the data on the current studies aimed at developing anti-Helicobacter pylori vaccines. Unfortunately, no vaccines recommended for use in human are available now, despite a more than 30-year history of their development and a great body of evidence on vaccine efficiency in animals. Mechanisms underlying vaccine-related effects in animals and human are poorly determined and expect to be further clarified. Moreover, side effects related to vaccines have not investigated in detail. A long-lasting stay of H. pylori in the gastric lumen restricts potential protective effects of host cellular immunity (an effect is mainly associated with antibodies and antimicrobial peptides), that results in low efficacy of systemic immunization and weak immune response. In addition, further complications in developing natural and artificial (vaccination) immune response may be due to the high pathogen variability and low immunogenicity of related antigens. A choice of antigen is crucial upon generating any vaccine.