This article reviews evidence and presents a hypothesis regarding the effects of stress on motivated behaviour, and in particular the observation that stress can have both motivationally inhibitory and motivationally facilitatory effects. This issue will be addressed with regard to psychostimulant self-administration, and the role that the neurobiological mechanisms underlying motivated behaviour are thought to be involved in the evolution of addictions. Evidence from animal studies shows that stress and stress-related hormones such as corticosterone can facilitate mesolimbic dopamine function and the behavioural effects of psychostimulants, particularly at lower levels of stress. Conversely, higher levels of stress can inhibit motivated behaviour, and evidence is presented that this may occur in part through the effects of the neuropeptide cholecystokinin (CCK), acting through CCK-B receptors in the nucleus accumbens. Individual differences in endogenous CCK and dopamine systems are hypothesized to be important modulators of individual differences in motivated behaviour.