The colonization of () in human gastric mucosa is highly associated with the occurrence of gastritis, peptic ulcer, and gastric cancer. Antibiotics, including amoxicillin, clarithromycin, furazolidone, levofloxacin, metronidazole, and tetracycline, are commonly used and considered the major treatment regimens for eradication, which is, however, becoming less effective by the increasing prevalence of resistance. Thus, it is urgent to understand the molecular mechanisms of pathogenesis and develop alternative therapeutic strategies. In this review, we focus on the virulence factors for colonization and survival within host gastric mucosa and the host antimicrobial responses against infection. Moreover, we describe the current treatments for eradication and provide some insights into new therapeutic strategies for infection.