The macrolide clarithromycin has emerged as the most important antibiotic in combined therapy for eradication of H. pylori infection[1,2]. However, concerns about increasing clarithromycin resistance in H. pylori and its impact on the efficacy of eradication therapy have been raised since its widespread acceptance in H. pylori therapy[3,4]. Here, we sought to review the geographic prevalence of clarithromycin resistance in H. pylori and its molecular mechanisms, and assess the clinical relevance of clarithromycin resistance. Geographic prevalence of clarithromycin resistant H. pylori The worldwide, prevalence of primary (pre-treatment) clarithromycin resistance to H. pylori ranges from 0. 8% to 18% (Figure (Figure11)[5-29]. The reported prevalence in China is between 4.8% and 7.5%, while the rate in Australia ranges from 6.1% to 7.8%[5,6,11,12]. Figure 1 Worldwide prevalence of clarithromycin resi stant H. pylori strains. Each of these studies included at least 50 strains. The number after each country is the reference number. Molecular mechanisms of clarithromycin resistance Versalovic et al[30] were the first to identify an A→G transition mutation within a conserved loop of 23S rRNA of H. pylori, and its association with clarithromycin-resistance. The mutation occurs commonly at two gene posi tions cognate with positions 2058 and 2059 of Escherichia coli-23S rRNA, whichwere re-named 2143 and 2144, and now revised as 2142 and 2143, respectively[4,31]. Point mutations may occasionally occur at other positions, and can be a transition (A→G) or a transversion (A→C), but the transition is far more frequent[4,32-35]. Moreover, Versalovic et al[32] also obser ved that the A2142G mutation was associated with a high level of resistance (MIC > 64 mg/L) than the A2143G mutation[32]. These observations are s upported by others studies[33,36]. It has been reported that macrolide-resistance was not stable in some strains of H. pylori in vitro[17]. This phenomenon was also observed in vivo; i.e., strains developed resistance post-treatment and then reverted to being susceptible after a period of follow-up[17,30]. Versalovic et al[30] cultured five genotypically identical isolates subsequentially from one patient before and after treatment with clarithromycin alone. They observed that the first two post-treatment isolates with a low-level clarithromycin resistance had an A2143G mutation, which was not present in the susceptible pretreatment isolate or in the last two post-treatment isolates with reverted susceptibility[30]. This suggests that the mutation may be unstable[35]. However, Hulten et al[35] reported that clarithromycin resistance was stable after 50 subcultures in vitro, which is consistent with other studies[37]. Cross-resistance between macrolides in H. pylori has been observed[12,17,30]. Generally, H. pylori strains resistant to clarithromycin are also resistant to erythromycin, azithromycin and roxithromycin or vice versa. These observations have been confirmed at the molecular level[36].