The ability of proteases to regulate cell function via protease-activated receptors (PARs) has led to new insights about the potential physiological functions of these enzymes. Several studies suggest that PARs play roles in both inflammation and tissue repair, depending on the cellular environment in which they act. The recent detection of PARs on peripheral and central neurons suggests that neuronal PARs might be involved not only in neurogenic inflammation and neurodegenerative processes, but also in nociception. Thus, the list of potential roles for PARs has lengthened considerably and their physiological course of action might be much broader than initially anticipated.