Behçet disease (BD) is a multifactorial inflammatory disorder classified in systemic vasculitides. Familial aggregation, peculiar geographic distribution, and association with HLA-B*51 support the role of genetics in its pathogenesis. The genome-wide association studies confirmed the importance of the HLA Class I region and revealed an epistatic interaction with ERAP1 variants and HLA-B*51. The ERAP1 variants-associated peptidome possibly contributes to pathogenesis by activating cytotoxic T-cell response or loading inappropriate peptides with lower affinity to HLA molecules, which may result in unfolded protein response. Several non-HLA gene associations were also identified, and some of them, such as associations with IL12A, IL10, CCR1/CCR3, and STAT4 were found to be shared with a spectrum of disorders characterized by a tendency to aphthous ulcers. Genetic studies lacked enough power to explore the heterogeneity of clinical presentations, which may be associated with manifestation-specific genes or different environmental triggers activating organ-specific inflammation in a shared genetic background.