As with many events in the history of science, the development of the hypothesis that acetaldehyde is a plausible psychoactive substance with specific central effects (not related to its toxic- ity) has not been either incremental or progressive. Rather, it has evolved through a process of fits and starts. Initial clinical obser- vations suggesting that accumulation of acetaldehyde could be used as a therapy for alcoholism did not lead to a highly effective treatment, and in fact, it was noted early on that small amounts of ethanol consumed under these conditions (i.e., blockade of aldehyde dehydrogenase) could be perceived as being even more pleasurable ( Chevens, 1953 ). Although some laboratory data in animals appeared at that time ( Carpenter and Macleod, 1952), it took a decade for the pre-clinical studies to focus on the poten- tial importance of acetaldehyde. Since Myers proposed in the late 60’s that acetaldehyde could be a mediator of some of the effects of ethanol ( Myers and Veale, 1969), advances in this field have gone through a push-pull process.