The findings indicate that cannabinoids induce apoptosis, necrosis, autophagy, cell cycle arrest and exert significant interactions with tumor microenvironment. Cannabinoids should be rather considered as a part of multi-targeted anti-tumor therapy instead of being standalone agent. Moreover, cannabinoids are likely to improve quality of life in patients with cancer, due to different supportive effects, like analgesia and/or anti-emetic effects. CBD: The administration of CBD in mice with injected subcutaneously melanoma caused significant extension of survival time and decrease in tumor growth compared to the control animals without treatment. The combination of THC with CBD causes stronger inhibition of cell viability in both in vitro and in vivo studies.