Various reports have shown that cannabinoids (the active components of marijuana and their derivatives) can reduce tumour growth and progression in animal models of cancer, in addition to their well-known palliative effects on some cancer-associated symptoms. This Opinion article discusses our current understanding of cannabinoids as antitumour agents, focusing on recent insights into the molecular mechanisms of action, including emerging resistance mechanisms and opportunities for combination therapy approaches. Such knowledge is required for the optimization of preclinical cannabinoid-based therapies and for the preliminary clinical testing that is currently underway.