The principles of top-down and bottom-up processing are essential to cognitive psychology. At their broadest, most general definition, they denote that processing can be driven either by the salience of the stimulus input or by individual goals and strategies. Selective top-down attention, specifically, consists in the deliberate prioritizing of stimuli that are deemed goal-relevant, while selective bottom-up attention relies on the automatic allocation of attention to salient stimuli (Connor, Egeth, & Yantis, 2004; Schneider, Schote, Meyer, & Frings, 2014). Variations within neurotransmitter systems can modulate cognitive performance in a domain-specific fashion (Greenwood, Fossella, & Parasuraman, 2005). Noudoost and Moore (2011a) proposed that the influence of the dopaminergic neurotransmitter system on selective top-down attention might be greater than the influence of this system on selective bottom-up attention; likewise, they assumed that the cholinergic neurotransmitter system might be more important for selective bottom-up than top-down attention. To test this hypothesis, naturally occurring variations within the two neurotransmitter systems were assessed. Five polymorphisms were selected; two of the dopaminergic system (the COMT Val158Met polymorphism and the DAT1 polymorphism) and three of the cholinergic system (the CHRNA4 rs1044396 polymorphism, the CHRNA5 rs3841324 polymorphism, and the CHRNA5 rs16969968 polymorphism). It was tested whether these polymorphisms modulated the performance in tasks of selective top-down attention (a Stroop task and a Negative priming task) and in a task of selective bottom-up attention (a Posner-Cuing task). Indeed, the dopaminergic polymorphisms influenced selective top-down attention, but exerted no effects on bottom-up attention. This aligned with the hypothesis proposed by Noudoost and Moore (2011a). In contrast, the cholinergic polymorphisms were not found to modulate selective bottom-up attention. The three cholinergic polymorphisms, however, affected the general response speed in the Stroop task, Negative priming task, and Posner-Cuing task (irrespective of attentional processing). In sum, the findings of this study provide strong indications that the dopaminergic system modulates selective top-down attention, while the cholinergic system is highly relevant for the general speed of information processing.