Behçet’s disease (BD) is a chronic, immuno-inflammatory condition with a complex etiology that involves genetic predispositions, environmental triggers, and immune system dysregulation. BD’s genetic landscape is characterized by both HLA-associated and non-HLA genetic factors, with the HLA-B*51 allele being the most significant genetic association. Infectious agents, particularly Streptococcus sanguinis and Herpes simplex virus, and changes in the microbiota are highlighted as potential environmental triggers that can initiate or exacerbate the disease in genetically predisposed individuals. BD exhibits features of both autoimmune and autoinflammatory diseases, making its classification challenging. The disease is characterized by an exaggerated innate immune response, with neutrophil hyperactivity and elevated pro-inflammatory cytokines, alongside abnormalities in the adaptive immune response, including dysregulated T and B cell activity. The vasculitic component of BD involves blood vessels of all sizes and is driven by mechanisms beyond traditional immune complex-mediated inflammation. Key processes include endothelial cell activation leading to thrombosis (immunothrombosis), excessive production of reactive oxygen species, and neutrophil extracellular traps (NETosis), contributing to inflammation and vascular damage. Historically classified among seronegative spondyloarthropathies and later considered within the realms of autoimmune and vasculitic diseases, BD is now suggested to be an MHC-I-opathy. This classification reflects shared characteristics with diseases involving MHC class I antigen dysregulation, bridging autoimmune and autoinflammatory disease features. Understanding the pathogenesis of BD is crucial for developing targeted therapies. While the multifaceted nature of the disease complicates treatment, understanding the genetic, environmental, and immunological factors provides hope for more effective interventions.