The discovery of proteinase-activated receptors (PARs) in the nervous system has led to new insights about the potential physiological functions of these enzymes, which were traditionally considered merely as degradative molecules. This review summarizes evidence that proteinases, through activation of PARs, interact with the peripheral nervous system (PNS), playing roles in neurogenic inflammation, pain perception, secretory and motor functions, as well as in the response to nerve injuries. Activation of PARs interferes with numerous physiological events that are under tight neural control, in addition to modulating nerve survival. New potential roles are suggested for members of the PAR family, highlighting proteinases and their receptors as potential therapeutic targets for diseases associated with PNS activation.