Opioids are widely used as painkillers and anesthetics. Though we use opioids to relieve pain, these drugs can induce mood elevation, dependency, and withdrawal symptoms. This is why opioids are controlled-substances. Most physicians think that some substances should be controlled if they have opioid-like pharmacological properties, especially a long duration, preservation of respiration, and dependency. It is noteworthy that short-acting substances, such as midazolam and thiopental, are included in controlled substances. Their abuse is very dangerous because they frequently induce severe respiratory depression due to a narrow therapeutic window. Teaching point of this article is that designation of a new drug as a controlled substance requires scientific evidence of its link to dependency and/or withdrawal symptoms. However, this does not require abusers' convenience (long duration) or safety (maintenance of respiration). The authors present the addiction and abuse patterns of propofol as an reasons for the Korean Food and Drug Administration to designate propofol as a controlled substance. As a future study, an animal and/or a clinical model for dependency is needed to identify addictive substances. Though several neurotransmitters and their loci in the central nervous system have been studied, the precise mechanism for addiction is unknown. Also, it should be recognized that the potential for drug addiction and abuse could be masked in the early marketing period of a new drug. Physicians should monitor patients' responses carefully when they deal with the drug.