The scholarly open access drug dependence journals publish latest and up-to-date information on drug dependence and abuse, and substance dependence. Articles published in this journal are freely available for the readers. Researchers, professionals, counselors, administrators, social workers and other users can advance their research work, by accessing these articles freely. Openly accessing and downloading the articles will increase the journal impact factor which determines the journal quality. Most theories of drug tolerance and dependence stress the physiological consequences of repeated pharmacological stimulation. There is considerable evidence, however, that the organism’s experience with the drug administration environment, as well as the drug, often importantly contributes to tolerance and dependence. The role of such environmental cues has been elaborated in a model which emphasizes Pavlovian conditioning principles. This account is based on the work of a number of investigators, but primarily Wikler (e.g., 1973, 1977, 1980), who have stressed the contribution of pharmacological learning to drug effects. This chapter describes the conditioning theory of tolerance, summarizes the data which supports the theory, discusses the relevance of the theory to drug dependence, and presents the implications ofthe theory for the treatment of drug abuse. Since some of the material has been summarized previously (Hinson and Siegel, 1980; Siegel, 1978a, 1979 b), this chapter emphasizes developments subsequent to earlier reviews.