Pain is relatively refractory to most of the current analgesics, emphasizing the importance of identifying novel pharmacological agents. Thus, modulation of the cannabinoid system is a new therapeutic approach. This could be performed at several levels. For endogenous cannabinoids, it would be a modulation of their synthesis, release, cellular uptake, metabolism or interactions with cannabinoid receptors. Many recent clinical studies investigating the role of cannabinoids in various pain syndromes demonstrated overall positive results. Nevertheless, cannabis and cannabinoids as analgesic agents have not been yet unequivocally established. Targeting preferentially peripheral cannabinoid receptors to avoid unwanted psychotropic effects is a new interesting avenue requiring further investigation.