Pemphigus vulgaris (PV) is a rare autoimmune disease due to the production of pathogenic autoantibodies directed against desmoglein 1 and 3, usually affecting both skin and mucous membranes. Recently, rituximab, a chimeric IgG1 monoclonal antibody which targets the CD20 molecules have been regarded as a promising treatment for PV. In this study, a systematic review was conducted to conclude on how and which PV patients could benefit from rituximab infusion. Search in PubMed results in 114 relevant studies, which met the criteria. Total of 1085 PV patients with different conditions, including unresponsive childhood/juvenile or adult PV patients, women of childbearing age, those with chronic infections with the risk of reactivation have been evaluated. Although the majority of these patients well responded to rituximab, some of them did not respond, and the paucity of patients experienced exacerbation of disease. In addition to the rituximab monotherapy or its combination with conventional therapies, different novel combination therapies of rituximab with immunoadsorption and/or IVIg have shown promising results. Moreover, using rituximab as the first-line treatment has emerged recently. Pneumocystis carinii pneumonia and septicemia were found as the two fatal and serious adverse events associated with rituximab. Moreover, development or reactivation of herpes simplex and herpes zoster and cytomegalovirus should be warned. Similar to the adults, those with childhood and juvenile PV could be successfully treated with rituximab. Although rituximab seems to trigger reactivation of chronic infections, such as viral hepatitis and HIV infection, no related report was found. Administration of rituximab in approximately ten months before conception also was found safe and effective for a successful pregnancy. In conclusion, rituximab is very effective in adult and childhood/juvenile PV. However, there is a risk of not responding, exacerbation of disease and development of fatal infections. Moreover, it seems to be a promising first-line treatment for refractory PV.