Helicobacter pylori (HP) infection is closely associated with the occurrence of such common upper gastrointestinal diseases as chronic gastritis, peptic ulcer and gastric cancer. However, even with the currently most effective treatment regimens, approximately 10% to 20% of patients still fail to obtain eradication of the infection and remain HP positive. So the eradication of HP infection remains one of the major challenges in the medical field. This article aims to introduce the evidence for the choice of the second-line regimens after the failure of the first therapy. And the evidence includes the quadruple therapy proposed by the Maastricht III Consensus and the triple regimens with different antibiotics in all kinds of randomized clinical trials.