The recently-discovered class of toll-like receptors (TLRs) play an essential role in the complex defence system against microorganisms. TLRs are the first to detect potential pathogens, initiate immune responses and form the crucial link between the innate and acquired immune systems. TLRs also play an important role in the pathophysiology of infectious diseases, inflammatory diseases such as Crohn's disease and atherosclerosis, and possibly play a role in autoimmune diseases. Common polymorphisms in TLR genes are associated with predisposition to severe infections. Drugs that target the TLRs offer new opportunities for the development of therapeutics against a wide variety of diseases such as sepsis syndrome, asthma, inflammatory-bowel diseases and cancer. The first drug that works by modulating the TLR response has already been registered.