Tolerance and sensitization are relatively simple manifestations of learning and memory that refer to decreases and increases in the strength of a response to a stimulus induced by past experiences with the same or related stimuli. In the context of the study of drugs, tolerance refers to the decreased effectiveness of a given drug with repeated administration; sensitization to the increased effectiveness with repeated administration. Tolerance usually involves active adjustments or adaptation to the drug-induce disturbances of function, either within cells or within a neural system. In situations involving inter-neuronal events, these processes of adjustment may take the form of learned modifications that can be re-evoked on future occasions by events that co-occurred at the time of the original modifications. Sensitization, defined as the enhancement of a directly elicited drug effect, though adaptive, appears to represent facilitation within a system, making the effect easier to elicit on future occasions. Like tolerance, sensitization of a drug effect can become linked to the events that co-occurred when the effect was originally elicited, making it possible for sensitization to come under selective event control. This paper is concerned with factors that affect whether tolerance and/or sensitization to the various effects of drugs will develop and be expressed, and with the variety and levels of mechanisms responsible for tolerance and sensitization under different conditions of exposure.