Cognitive deficits following acute administration of corticosteroids have been described in experimental animals and humans. In both populations, an inverted-U shape relationship has been reported between the dose of corticosteroids administered and the nature and extent of the cognitive deficits induced by corticosteroids. Further studies in animals have revealed a two-level recognition system for adrenal steroids, which was later more clearly resolved into two receptor types: Type I and Type II adrenal steroid receptors. The demonstration of an inverted-U shape relationship between corticosteroids and cognitive process leads to the question as to whether this relationship is generated via the two receptor types, exerting effects either via competing or opposing processes or via a more synergistic interaction. In this article, we review the effects of corticosteroids on animal and human cognition and propose a theoretical framework that leads to testable predictions regarding the acute effects of corticosteroids on cognitive function. We also discuss some methodological and experimental factors that might explain some discrepancies in data obtained from animals and humans. Furthermore, we suggest new experimental protocols for use in humans, based on animal literature, that could help resolve these discrepancies and assess more clearly the nature of the cognitive deficits induced by acute administration of corticosteroids.