The purpose of this review is to gain more insight in the neuropathology of pathological gambling (PG) and problem gambling, and to discuss challenges in this research area. Results from the reviewed PG studies show that PG is more than just an impulse control disorder. PG seems to fit very well with recent theoretical models of addiction, which stress the involvement of the ventral tegmental-orbito frontal cortex. Differentiating types of PG on game preferences (slot machines vs. casino games) seems to be useful because different PG groups show divergent results, suggesting different neurobiological pathways to PG. A framework for future studies is suggested, indicating the need for hypothesis driven pharmacological and functional imaging studies in PG and integration of knowledge from different research areas to further elucidate the neurobiological underpinnings of this disorder.