Regulation of drug intake refers to the maintenance of relatively constant levels of drug over a specified time period. An understanding of regulation of drug intake may be critical in determining how drugs function as reinforcers and how their reinforcing effects may be modified. However, little is known about regulation of drug intake, and the mechanisms underlying it are poorly understood. Three mechanisms that have proposed to account for findings of regulation of drug intake were discussed to determine their relevance for drug-reinforced responding. These mechanisms include aversive effects, direct effects, and satiation. Although a greater role for satiation was supported in this review, drugs may vary on the degree to which they can produce satiation and whether satiation acts in concert with either the aversive effects or the direct effects of drugs is unclear.