Here, we have highlighted clinical evidence supporting the therapeutic use of cannabinoids in medicine for the treatment of diseases. The involvement of the endocannabinoid system in the physiological functions and in the pathological state of diseases has allowed the development of more efficacious and safer cannabinoid-based drugs. Further research is needed to identify promising therapeutic targets within the endocannabinoid system and to investigate the pharmacological effects of minor phytocannabinoids. Clinical results with preparations containing ?9-THC, CBD, and palmitoylethanolamide are greatly promising for several disorders (neurodegenerative diseases and neuropathic pain, among others). In cancer, the therapeutic utility is still limited to their analgesic and antiemetic properties such as for nausea and vomiting. In conclusion, further exploration and understanding of the potential risks and benefits of cannabinoid-based drugs is needed through large-scale clinical trials to evaluate their therapeutic potential.