Decision-making in gambling involves evaluation of the likely consequences of one's actions and a consideration of the desires for immediate and long-term gratification. These processes require intact brain mechanisms which have been investigated through the use of cognitive tests and neuroimaging studies, primarily functional magnetic resonance imaging studies. Recently, contrary to the 'emotion versus cognition' hypothesis, it has been suggested that the cognitive and emotional components of decision-making are incorporated through cortex-subcortex interactions and this interplay will be discussed and critically reviewed, using the exemplars of decision-making under ambiguity and regret. This review explores the involvement of specific brain regions and the neurotransmitters which regulate these areas, primarily focusing on the integrated and distinct roles of the orbitofrontal cortex and the ventromedial prefrontal cortex. The mediatory roles of other important brain regions, such as the amygdala and the cingulate cortex, will also be examined. This review highlights the considerable implications of the decision-making psychological process in understanding daily human behaviours, addictions and pathological gambling.