Cannabinoids, their receptors and their metabolizing enzymes are emerging as a new regulatory system, which is involved in multiple physiological functions. Normal prostate tissue expresses several constituents of the endocannabinoid system including the CB(1) receptor, receptors belonging to the transient receptor potential family and fatty acid amide hydrolase, a hydrolyzing enzyme, all of which have been localized in the glandular epithelia. Accumulating evidence indicate that the endocannabinoid system is dysregulated in prostate cancer, suggesting that it has a role in prostate homeostasis. Overexpression of several components of the endocannabinoid system correlate with prostate cancer grade and progression, potentially providing a new therapeutic target for prostate cancer. Moreover, several cannabinoids exert antitumoral properties against prostate cancer, reducing xenograft prostate tumor growth, prostate cancer cell proliferation and cell migration. Although the therapeutic potential of cannabinoids against prostate cancer is very promising, future research using animal models is needed to evaluate the influence of systemic networks in their antitumoral action.