Serine proteases exert a variety of functions in the body; food digestion, regulation of other proteins and modification of extracellular matrix. Cumulative evidence has shown the importance of serine proteases in the nervous system as well. It has been shown that three serine proteases, thrombin, plasminogen activators and neuropsin, have functional roles in neural plasticity. Most of the actions of thrombin are thought to be mediated by its specific receptors. Thrombin reverses neurite outgrowth of serum-deprived neuroblastoma cells, and induces protective and apoptotic effects on neurons and glial cells depending on concentration and time. Tissue-type and urokinase-type plasminogen activators (tPA and uPA) distribute broadly in the brain. tPA and uPA exert a variety of functions during development. These proteases also function in long-term potentiation and kindling formation. Furthermore, tPA is essential to excitotoxic neuronal cell death. Neuropsin is a serine protease expressed in the limbic system of the brain. Kindling induced neuropsin mRNA and protein expression and anti-neuropsin antibody ameliorates kindling epilepsy. The possible roles of these proteases in neural plasticity are reviewed here.