Although a number of previous review articles cover the effects of psychostimulant drugs on the operant or schedule-controlled behavior, none of those had focused on the effects of amphetamine and cocaine on operant behavior exclusively maintained by differential reinforcement of low-rate response (DRL). This review (a) summarizes research on the psychopharmacology of amphetamines and cocaine that has been conducted using DRL behavior, (b) discusses the potential neural substrates underlying the aforementioned drug-induced behavioral alterations on the basis of the data from lesion studies, and (c) highlights two major behavioral components, behavioral inhibition and temporal control of DRL responding, that are altered by amphetamines and cocaine. Amphetamines and cocaine affect the development and/or performance of DRL behavior in dose related ways that can be differentiated on the basis of the specific types of behavioral alterations. In general, with the moderate but effective doses, these drugs significantly increase the total number of responses and decrease the number of reinforced responses. Although the burst responses with very short inter-response times (IRT's) are more likely increased by these drugs, this aspect of the drugs' effects were found to vary across studies that used different experimental procedures of shaping up or training the subject to perform DRL behavior. Both amphetamine and cocaine produce a leftward shift on the IRT frequency distribution curve compared to vehicle treatment. The effects of amphetamines and cocaine on DRL behavior as reviewed here further highlight the need for additional research to probe neurobehavioral mechanisms that may underlie DRL behavior as manifested by both burst responding and timing the emission of the operant response.