Background: Changes in neuropsychological and emotional systems are associated with substance dependence and reduce the chance of successfully maintaining abstinence after treatment. Impulsivity is strongly associated with substance dependence and is a risk factor for development, a consequence of excessive use and a marker for poor treatment outcomes. The focus of this thesis is impulsivity, as well as emotional and motivational factors, in the context of harmful substance use and dependence. The thesis is formed of two parts; the first (Studies 1 and 2) focusses on the multi-faceted role of impulsivity in substance dependence. The second part (Studies 3 and 4) investigates negative reinforcement and automatic approach and avoidance behaviour in heavy alcohol use. Study 1: A multi-dimensional investigation of impulsivity in abstinent substance dependent individuals using three complementary techniques: self-report, behavioural and neural measures. Results suggest that self-report measures of impulsivity are more sensitive in abstinent individuals than behavioural or fMRI measures. Study 2: An alternative approach to the classification of substance dependent individuals; using Latent Profile Analysis, abstinent substance dependent participants from Study 1 were regrouped based on personality risk factors rather than primary dependence. Important differences were detected within a previously undifferentiated group of abstinent substance dependent individuals; notably the greater incidence of childhood adversity and stimulant dependence history in one group, while the other did not differ from controls.Study 3: A behavioural investigation of the effect of stress induction on automatic approach and avoidance in heavy drinking individuals compared to light drinkers. Results indicated no differential effect of stress. These findings may suggest that the behaviour of older, more established heavy drinkers is comparable to that of alcohol dependent participants and reflects an advanced stage along the spectrum of alcohol use and dependence.Study 4: An fMRI investigation conducted on a subset of participants from Study 3 using neuroimaging paradigms to assess automatic approach and avoidance behaviour in heavy drinking individuals compared to light drinkers. Results can be interpreted to suggest that heavy drinkers approach alcohol in a less controlled manner than light drinkers, and that trait anxiety may be involved in the extent of avoidance behaviour. Conclusions: Although there are more questions raised by this research than are answered, some general conclusions can be drawn. Specifically, impulsivity measures need to be made more appropriate to all stages of substance use and dependence. Furthermore I propose a longitudinal theory of substance use and dependence with different neurocognitive profiles at each stage, as well as individual differences throughout the trajectory. This has implications for future addiction research that should enable better understanding for the benefit of clinical practice and treatment of substance related disorders.