Henoch-Schönlein purpura (HSP) is the most common form of systemic vasculitis of unknown etiology. This study aimed at reviewing published studies investigating the association of genetic polymorphisms with HSP and its severity. We systematically reviewed all published data on genetic risk factors for HSP by searching MEDLINE. We also performed a meta-analysis of association studies of HLA-DRB1-01, 07, and 11, angiotensin I-converting enzyme (ACE) insertion/deletion (I/D) polymorphism. We identified 45 studies investigating polymorphisms in 39 genes in association with HSP and/or its severity. Most of these genes are involved in immunological and/or inflammatory responses or vasomotor regulation. Most results were negative. The most convincing finding is the association of HLA-DRB1 01, 07, and 11 with HSP susceptibility. The overall odds ratios (ORs) for the three loci were significant for HSP: HLA-DRB1 01 (OR = 1.805, 95 % CI 1.259-2.588, p = 0.0012); HLA-DRB1 07 (OR = 0.671, 95 % CI 0.469-0.961, p = 0.058); HLA-DRB1 11 (OR = 2.001, 95 % CI 1.50-2.67, p = 0.027). Genetic regulation of endothelial function, such as polymorphisms in genes coding rennin-angiotensin system (RAS) components, endothelial nitric oxide synthases, Inter-Cellular Adhesion Molecule 1, and vascular endothelial growth factor, could also confer effect on HSP. In addition, MEFV, whose mutations cause familial Mediterranean fever, could be an important candidate gene for HSP. Further large studies are required to investigate the association between genetic polymorphisms and HSP. Alternative approaches, such as genome-wide association study, are necessary to help to identify genetic risks for HSP.