The addictive potential of nicotine is clearly recognized by the tenacity of tobacco smoking for most users, and has prompted extensive psychopharmacological studies in animals. In parallel, the interaction of nicotine with the many subtypes of its eponymous receptor has been the focus of molecular and cellular investigations. More recently, a convergence of these approaches has been stimulated by the generation of transgenic animals, which facilitates analysis of the impact of molecular changes on behaviour. Nicotine, like other addictive drugs including psychomotor stimulants, promotes dopamine release in the nucleus accumbens. This transmitter system has been a major focus of both neurochemical and behavioural investigations, although recently the pre-eminence of this system in nicotine dependence has been challenged. Complexities in the brain circuitry (including the subdivisions of the nucleus accumbens) and differences between behavioural models help to rationalise the current controversy.