Behçet's disease (BD) is a systemic vasculitis with unclear etiology and pathogenesis. Although several viral and bacterial causes have been investigated in detail for several years, of late it is widely accepted that microorganisms may play a role as a trigger, or as a cross-reactive antigens that interfere with self-antigens, such as heat-shock proteins. Genes such as HLA-B51, MICA and TNF, considered to play a crucial role in the pathogenesis of BD, are located in the major histocompatibility complex (MHC). However, it has been accepted that, only HLA-B51 is directly related with pathogenesis of the disease, and others have strong linkage disequilibrium with HLA-B51. Some other genes such as IL1, Factor V and ICAM-1, KIR and eNOS assumed to take a part in the pathogenesis are settled out of the MHC region. In patients with BD, several abnormalities in innate and acquired immunity were detected. Mainly, the hypersensitivity of T lymphocytes to different types of antigens plays a critical role in the pathogenesis. However, it is not clear that whether defective signal transduction or antigen presenting cell (APC) dysfunction is responsible for T cell hypersensitivity. Cytokines and chemokines secreted from APCs and T cells are suggested to cause the neutrophil hyperactivation. Activated neutrophils secrete some cytokines, which prime themselves and also stimulate Th1 cells. These relationships among APCs, Th1 lymphocytes and neutrophils constitute the basis of immune responses in BD. In this review, we focus on the possible role of APC in the pathogenesis of BD with an attempt to take attention of researchers in this field to these cells at the crossroads of innate and adaptive immunity, and discuss other potential contributors including cells of the immune system and mediators.