Lithium, which has been used in the psychiatric domain for many years, is showing interesting properties as a neuroprotective agent against different apoptotic insults. These neuroprotective effects have been explained by its action in signaling pathways implicated in apoptosis and cell survival. Studying the action of lithium in these signaling pathways, emerging data show lithium as an inhibitor of the dephosphorylation events. The importance of phosphorylation and dephosphorylation in intracellular signaling pathways has been long recognized, although attention has focused mainly on kinases, which have become the second most important group of drug targets. However, recent studies are highlighting the importance of serine / threonine protein phosphatases in apoptosis. The effect of lithium on serine / threonine protein phosphatases needs further study, but lithium is pointing out these enzymes as potential targets for novel therapeutics against neurodegenerative diseases.