Central serous chorioretinopathy (CSC) is a serous macular detachment that usually affects young people and leads fortunately to a spontaneous resolution and a good visual prognosis in most patients. Nevertheless, although in a small percentage of subjects only, it may also develop a chronic or progressive disease with widespread decompensation of the retinal pigment epithelium (RPE) and severe vision loss. The aetiopathogenesis of the disease is still not completely understood and no effective treatment is available at this time. However, an interesting association has been recently highlighted between CSC and the Helicobacter pylori infection. In particular, in a first case report recurrences of the disease were always associated with HP-positivity whereas improvements of both retinal findings and visual acuity were significantly correlated with a successful eradication of the bacterium using the conventional antimicrobial triple-therapy. In a second study, the prevalence of HP infection was found to be significantly higher in CSC-affected subjects compared to age- and sex-matched controls from the same country. Much speculation surrounds the role potentially played by HP in determining CSC. In particular, CSC seems not to be more a merely RPE disease but the final result of a general involvement of the choroidal microcirculation. In fact, several vascular abnormalities, such as localized vasoconstriction and impaired fibrinolysis, have been demonstrated during CSC whose end-points might be a focal occlusion of the choriocapillaries with decreased foveal choroidal blood flow, secondary RPE defects and serous macular detachment. Moreover, a HP-dependent immune mechanism, based on a molecular mimicry between pathogenic antigens expressed on the bacterium and homologous host proteins (e.g., those of the endothelial vascular wall), might also be involved in the pathophysiology of CSC. In this case, a genetically determined susceptibility of the subject could be an important and limiting factor. Although further multicenter, randomized, case-control trials are necessary to confirm the role potentially played by the HP infection in the pathogenesis of CSC, if this hypothesis would be confirmed in the near future, a novel antimicrobial approach to the disease might be possible waiting for a successful vaccine therapy that will surely stimulate the scientific interest of many authors.