Cholinergic systems have been linked to cognitive processes such as attention, learning and mnemonic function. However, other neurotransmitter systems, such as the serotonergic one, which may have only minor effects on cognitive function on their own, interact with cholinergic function and their combined effects may have marked behavioural actions. Some studies have dealt with serotonergic-cholinergic interactions, but it is unclear whether both systems affect cognition directly or whether interactions at a behavioural level result from additional alterations in non-cognitive factors. This distinction is difficult, since it is possible that the diverse cholinergic and serotonergic systems serve different roles in the mediation of cognitive processes, both at the neuroanatomical and neurochemical level. Nevertheless, it is possible that cholinergic systems primarily alter accuracy in cognitive tasks, whereas serotonergic neurotransmission modulates behaviour by altering bias (motivation, motor processes). Whether serotonin alters accuracy or bias, however, may also depend on the cognitive process under investigation: it is suggested that attention, stimulus processing and/or arousal can be influenced by both cholinergic and serotonergic systems independently from each other. Cholinergic and serotonergic projections to cortex and thalamus may be of importance in the mediation of these cognitive processes. Serotonergic-cholinergic interactions could also be of importance in the mediation of learning processes and trial-by-trial working memory. The data available do not allow an unambiguous conclusion about the role of these interactive processes in the mediation of long-term reference memory. These processes may rely on serotonergic-cholinergic interactions at the hippocampal level. It is concluded that serotonergic-cholinergic interactions play an important role in the mediation of behavioural, including cognitive, performance, but that further studies are necessary in order to elucidate the exact nature of these interactions.