Toll-like receptors (TLRs) represent one of the families of pattern recognition receptors (PRRs) and are an important part of the innate immune system . They are able to recognise various molecular patterns (MPs) in the host organism -damage/danger-, microbial/microbe-, pathogenor xenobiotic-associated (DAMPs, MAMPs, PAMPs, or XAMPs, respectively) . Recognition of those MPs activates downstream signalling cascades that lead to the induction of the innate immune system . In humans, TLRs comprise ten functional members (TLR1-10) which share similar domain organisation: an N-terminal domain containing the leucine-rich repeats (LRR), a single transmembrane helix (TM), and a C-terminal cytoplasmic Toll-interleukin-1 receptor (TIR) domain (Figure ). TLR7-9 possess an additional long-inserted loop region (so-called Zloop) in their LRR domain (Figure ) which needs to be cleaved proteolytically. The LRR domain is responsible for ligand recognition, while the TIR domain interacts with adaptor proteins and is responsible for initiating signal transduction. A characteristic feature of the TIR domain in all TLRs is the conserved and functionally important BB-loop (Figure ). TLRs are expressed either on the cell surface (TLR1, 2, 4, 5, 6, 10; occasionally TLR7) or in the various intracellular compartments (TLR3, 7, 8, 9; occasionally TLR4). The location of TLRs determines the spectrum of ligands they are able to recognise. For instance, TLRs expressed on the cell surface primarily recognise microbial membranes and/or components of the cell wall, while intracellular TLRs principally recognise nucleic acids . The full list of the recognised ligands is much larger and has been discussed in several papers . The binding of ligands to a TLR either induces the formation of a receptor dimer or changes the conformation of a preexisting dimer (Figure ) which subsequently allows adaptor proteins to bind and trigger an immune response . TLRs can recruit various adaptor proteins, however, myeloid differentiation primary-response protein 88 (MyD88) and TIR domain-containing adaptor protein inducing interferon-β (TRIF) are the most important ones. Two distinct signalling pathways used by TLRs start from them -MyD88-dependent and TRIF-dependent pathways. In general, the MyD88-dependent pathway is utilised by all TLRs, except TLR3, and leads to the production of various proinflammatory cytokines. The TRIF-dependent pathway is utilised by TLR3 and 4 and is associated with the stimulation of type-I interferon (Figure ). Toll-like receptors are a potential therapeutic target in various diseases and conditions. Thus, searching for and designing compounds which can act as agonists or antagonists is the objective of many studies. The distinction between agonists and antagonists for TLRs is crucial since they are used to treat different conditions. For instance, TLR agonists have been developed to treat allergies, asthma, different types of cancer, and chronic infections by upregulating the innate immune system. Moreover, since TLRs induce the response of the body's defences, they are also promising targets for designing vaccines. On the other hand, TLR antagonists have been used to treat many inflammatory conditions such as acute/chronic inflammation, sepsis, chronic obstructive pulmonary diseases, cardiovascular diseases, neuropathic and chronic pain and various autoimmune diseases .