To evaluate the use of rituximab in the treatment of severe glomerulonephritis (GN) in order to prevent progression of kidney disease toward the end stage, we designed a multicenter, retrospective study in Saudi Arabia about the efficacy and safety of the use of "off label" rituximab in a variety of severe refractory GN to conventional treatment and the progression of kidney disease for at least one year of follow-up. All the patients had kidney biopsies before treatment with rituximab, and proteinuria and glomerular filtration rate (GFR) were followed-up for the period of the study. The immediate side-effect at the time of administration of rituximab included itching in three patients, hypotension in one patient and anaphylaxis in one patient (dropped out from the study). After the administration of rituximab in 42 patients and during the first six months of therapy, 16 (38%) patients had complete remission (CR), 13 (31%) patients had partial remission (PR) and 13 (31%) patients had no remission. The mean follow-up period for the patients was 19.0 ± 6.97 months (median 18.0 months). The long-term follow-up during the study period disclosed a good hospitalization record for almost all of the patients. Membranous GN (MGN) was the largest group in the cohort (58% of the patients), and we observed CR and PR in 40% and 28% of them, respectively, which was comparable with the previous experience with rituximab in MGN patients with more CR than PR in our cohort. We conclude that our study suggests the safety and efficacy of the use of rituximab in patients with refractory GN and that larger and long-term prospective studies are required to define the role of rituximab in the different categories of these diseases.