Toll-like receptor 3 (TLR3) recognizes viral double-stranded RNA and its synthetic analog polyriboinosinic:polyribocytidylic acid (poly(I:C)) and induces type I interferon (IFN), inflammatory cytokine/chemokine production and dendritic cell (DC) maturation via the adaptor protein TICAM-1 (also called TRIF). TLR3 is expressed both intracellularly and on the cell surface of fibroblasts and epithelial cells, but is localized to the endosomal compartment of myeloid DCs. Several studies in TLR3-deficient mice demonstrate that TLR3 participates in the generation of protective immunity against some viral infections. Involvement of TLR3-TICAM-1 in activation of NK cells and CTLs by myeloid DCs suggests that TLR3 serves as an inducer of cellular immunity sensing viral infection rather than a simple IFN inducer. In this review, we summarize the current knowledge on TLR3 and discuss its possible role in innate and adaptive immunity.