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Toll-like receptors (TLRs) play a crucial role in host defence and inflammation. Given that a significant amount of evidence implicates TLRs in the pathogenesis of immune diseases and cancer, and their activation occurs early in the inflammatory cascade, they are attractive targets for novel therapeutic agents. Potential therapeutics include TLR-targeted antibodies, small molecules and nucleic acid based drugs. Agonists are being tested in vaccines against hepatitis C and influenza as well as in allergic rhinitis and certain cancers. Antagonists are being tested in ischemia/reperfusion injury, systemic lupus erythematosus and psoriasis. The prospect of targeting TLRs in multiple pathologies continues to hold much promise.