Behçet's disease is a chronic inflammatory disorder of unknown etiology. It has long been postulated that immunological abnormalities, which are possibly induced by microbial pathogens in genetically susceptible individuals, are important in its pathogenesis. Recent findings have both supported the significance of genetic factors and better defined the nature of inflammation in Behçet's disease. Molecular genetic studies have strengthened the primary association of HLA-B51 with Behçet's disease. The exact pathogenic mechanism of the HLA-B51 molecule is still unknown, and its contribution to the overall genetic susceptibility to Behçet's disease is estimated to be less than 20%. Spontaneous and/or induced overexpression of pro-inflammatory cytokines (mainly Th1 type) from various cellular sources seems responsible for the enhanced inflammatory reaction in Behçet's disease, and it may be associated with the genetic susceptibility. An antigen-driven immune response superimposed on this primed-state and induced by heat shock proteins or other peptides from different strains of streptoccocci or other microbial agents has been suggested to trigger manifestations of Behçet's disease. Endothelial activation/injury and the resultant occlusive vasculopathy may also contribute to the tissue damage.