Progesterone exerts a variety of actions in the central nervous system under physiological and pathological conditions. As in other tissues, progesterone acts in the brain through classical progesterone receptors and through alternative mechanisms. Here, we review the role of progesterone as a regulator of kinases and phosphatases, such as extracellular-signal regulated kinases, phosphoinositide 3-kinase, Akt, glycogen synthase kinase 3, protein phosphatase 2A and phosphatase and tensin homolog deleted on chromosome 10. In addition, we analyzed the effects of progesterone on the phosphorylation of Tau, a protein that is involved in microtubule stabilization in neurons.