“Neurosteroids” accumulate in the central nervous system independently of supply by peripheral endocrine glands. Dehydroepiandrosterone (DHA) and pregnenolone (Δ5P) were first found in the rat brain. Then, a steroid biosynthetic pathway was demonstrated in oligodendrocytes, mostly by enzyme immunocytochemistry and biochemical studies in primary cultures of glial cells, where the formation, from appropriate radioactive precursors, of Δ5P, Δ5-pregn-3β,20α-diol (20α-DHΔ5P), progesterone (P), 5α-pregnane-3, 20-dione (5α-DHP) and 3α-hydroxy-5α-pregnane-20-one (3α, 5α-THP), as well as estrogen-induced progesterone receptor (PR) was observed. Several biological effects of neurosteroids have been observed, such as electrical stimulation of neurones, involvement in behavioral activities, modulation of GABA A -receptor (GABA A -R) function (potentiated by 3α,5α-THP and its 21-hydroxyderivative, antagonized by Δ5P- and DHA-sulfates) and growth/differentiation of glial cells in vitro . Preliminary findings suggest that the neurosteroid concept applies to all mammalian species, including man. Further investigations should assess the pathophysiological significance of the synthesis of neurosteroids and decipher their mechanisms of action via nuclear and membrane receptors.