Nicotine has a unique profile among drugs of abuse. To the noninitiated user, nicotine has powerful aversive effects and its relatively weak euphorigenic effects undergo rapid tolerance. Despite this, nicotine is commonly abused despite negative heath consequences, and nicotine users have enormous difficulty quitting. Further, nicotine is one of the most commonly co-abused substances, in that it is often taken in combination with other drugs. One explanation of this polydrug use is that nicotine has multiple appetitive and consummatory conditioning effects. For example, nicotine is a reinforcement enhancer in that it can potently increase the incentive value of other stimuli, including those surrounding drugs of abuse such as alcohol. In addition, nicotine also has a unique profile of neurobiological effects that alter regulation of alcohol intake and interoception. This review discusses the psychological and biological mechanisms surrounding nicotine's appetitive conditioning and consummatory effects, particularly its interactions with alcohol.