Given that PRRs including TLRs and their signaling pathways are highly conserved throughout evolution, the pharmacological exploitation of the TLR4 complex can be considered promising in the context of (i) chronic inflammatory disorders (atherosclerosis, arthritis, etc.); (ii) acute inflammation, i.e., SIRS and sepsis; (iii) airway inflammation of both chronic (asthma and allergy) and acute etiology (ALI); (iv) vaccine adjuvant development; and (v) oncological pathologies where both the activation and inhibition of TLR4 signaling could be of use as a stand-alone or adjuvant therapy. Here, TLR4 is linked to arthritic joint disease.