One of the main causes of death around the world is cancer. Although the development of antitumor drugs has increased life expectancy in these patients during the past decades, chemotherapy is associated to acute and long-lasting impactful side effects. The endocannabinoid system is formed by the cannabinoid receptors CB1 and CB2, the endogenous agonists of these receptors, and all the enzymes necessary for the metabolism of the endocannabinoids. The wide distribution of the endocannabinoid system and its involvement in the modulation of a wide range of biological processes highlight the great therapeutic potential of cannabis and cannabinoids in many diseases, including gastrointestinal alterations, pain, cachexia, or cancer. To date, only a few cannabinoid agonists have been approved for different pathologies, although in relation to cancer, only oral capsules and solutions based on synthetic analogues of Δ9-tetrahydrocannabinol have been approved for the treatment of chemotherapy-induced nausea and vomiting. Despite the vast positive results obtained from animal studies regarding the usefulness of cannabinoids to reduce other symptoms related to cancer and its treatment, such as neuropathic pain or cachexia, conflicting evidence exists in the clinical setting, due, mainly, to the lack of more high-quality clinical studies. Moreover, the psychotropic effects and immune suppression mediated by CB1 and CB2 agonists, respectively, arise safety concerns that need to be considered. In conclusion, although strategies aimed at modulating the endocannabinoid system can play a pivotal role in the treatment of different side effects associated to cancer chemotherapy, future studies will be needed to confirm their effectiveness and safety in the clinical setting.