Neurosteroids are concentrated within and are known to produce effects that modulate central nervous system function. Among the effects associated with the administration of the excitatory neurosteroid dehydroepiandrosterone sulfate (DHEAS), is the enhancement of memory.  The mechanism for this enhancement is not well understood, however, DHEAS can increase the release of acetylcholine (ACh) in the hippocampus of rats and also facilitate neurotransmission mediated by NMDA receptors.  Moreover, some cognitive effects of DHEAS are potentiated by the co-administration of steroid sulfatase inhibitors (SSI). Steroid sulfatase inhibitors can enhance hippocampal ACh as well as block scopolamine induced amnesia.  The studies reviewed in this article investigated whether acute and/or chronic peripheral administration of DHEAS or SSI could facilitate hippocampal neurotransmission and cognitive function following administration of the cholinergic antagonist scopolamine. The results demonstrated that DHEAS and SSI enhanced ACh release in the hippocampus and increased performance in cognitive tests including passive avoidance, Morris water maze and delayed matching to position T-maze.