Accumulating evidence suggests that serotonin may modulate cholinergic function in several regions of the mammalian brain and that these serotonergic/cholinergic interactions influence cognition. The first part of this review is an overview of histological, electrophysiological and pharmacological (in vitro, in vivo) data indicating that, in several brain regions (e.g., hippocampus, cortex and striatum), there are neuroanatomical substrates for a serotonergic/cholinergic interaction, and that alterations in serotonergic activity may induce functional changes in cholinergic neurons. In the second part, the review focuses on experimental approaches showing or suggesting that central cholinergic and serotonergic mechanisms are cooperating in the regulation of cognitive functions. These arguments are based on lesion, intracerebral grafting and pharmacological techniques. It is concluded that not all mnesic perturbations induced by concurrent manipulations of the serotonergic and cholinergic systems can be attributed to a serotonergic modification of the cholinergic system. The cognitive faculties of an organism arise from interactions among several neurotransmitter systems within brain structures such as, for instance, the hippocampus or the cortex, but also from influences on memory of other general functions that may involve cerebral substrates different from those classically related to mnesic functions (e.g., attention, arousal, sensory accuracy, etc.).