Toll-like receptors (TLRs) are highly conserved trans-membrane proteins that play an important role in the detection and recognition of microbial pathogens. The key product of TLR signalling in antigen presenting cells is the production of inflammatory cytokines and proteins. The TLR pathway plays an important role in mediating whole body inflammation, which has been implicated in the development of chronic disease. An accumulation of chronic, low-grade inflammation is common in individuals that live a sedentary lifestyle; however, the mechanism underlying this connection is not fully understood. There is evidence to show that TLRs may be involved in the link between a sedentary lifestyle, inflammation, and disease. Recent studies have shown that both acute aerobic and chronic resistance exercise resulted in decreased monocyte cell-surface expression of TLRs. Furthermore, a period of chronic exercise training decreases both inflammatory cytokine production and the cell-surface expression of TLR4 on monocytes. These effects may contribute to post-exercise immunodepression and the reported higher susceptibility to infection in athletes. However over the long-term, a decrease in TLR expression may represent a beneficial effect because it decreases the inflammatory capacity of leukocytes, thus altering whole body chronic inflammation. The precise physiological stimulus mediating an exercise-induced decrease in cell-surface TLR expression is not known; however a number of possible signals have been implicated including anti-inflammatory cytokines, stress hormones and heat shock proteins.