Place conditioning is among the most commonly used procedures to assess drug reward in animals. The procedure is used to study acquisition of conditioning, extinction, and reinstatement, to compare across drugs and doses of drugs, and to examine interactions between drugs and environmental or organismic variables. Studies using the procedure have provided a rich source of data regarding contextual conditioning in rodents, and most recently, in humans. Despite its widespread use, the place preference procedure has also raised theoretical and practical questions. Some of the questions are related to the procedural details and methods used: methodological variations on the procedure can affect the outcome and interpretation. In this review, we will examine some of the important methodological considerations in place conditioning with drugs and discuss how these have bearing on the results and conclusions. First, we will discuss what is being measured with place conditioning. Second, we will review the key phases of the procedure and methodological variations in the procedure that can influence the outcome. Third, we will describe place conditioning in humans and the unique methodological issues that arise in applying the procedure to humans. Finally, we will discuss potential limitations and future directions related to drug-induced place conditioning.