Toll-like Receptors (TLRs), the evolutionarily conserved molecules are identified as the pattern recognition receptors (PRRs) in vertebrates and invertebrates which recognize the pathogenassociated molecular patterns (PAMPs). The TLRs signaling is via interactions with adaptor proteins including MyD88 and toll receptor associated activator of interferon (TRIF). They__ampersandsignamp; directly detect the pathogen invasion and induce either immuno-stimulatory or immunomodulatory biological response. This ability of TLRs to modulate the immune system has been taken in concern in recent studies to develop an adaptive immunotherapy against cancer and several other neurological disorders. Moreover, to trace their auxiliary therapeutic effects, the TLR agonists are now undergoing the extensive clinical investigation. This review discusses the therapeutic potential of TLRs as Immunostimulators and Immunomodulators. Alongside, the association of TLRs with autoimmune responses and human diseases is also explored.