The psychedelic psilocybin and the entactogen 3,4-methylenedioxymethamphetamine (MDMA) are being scientifically studied again after a long hiatus, and especially for their potential in the treatment of psychiatric disorders. Their profound effect on cognitive, perceptual, and affective processes have led to several clinical studies during the last decade that have forced the reconsideration of the utility of these substances. The research includes clinical trials with psilocybin-assisted psychotherapy for depressive and anxiety symptoms, and MDMA-assisted psychotherapy for the treatment of post-traumatic stress disorder (PTSD). The results have shown a significant reduction in depressive and anxiety symptoms in psilocybin-assisted psychotherapy, and in PTSD symptoms in MDMA-assisted psychotherapy, with acceptable adverse effects. Moreover, the reductions in symptoms have been shown to be sustained several years later. Given the results indicate short- and long-term safety and efficacy, even for treatment resistant conditions, this suggest that these substances administered with psychotherapy are promising and deserve to be taken seriously as a therapeutic tool. The present thesis provides an overview of the latest clinical studies on the treatment of depression, anxiety, and PTSD with psilocybin and MDMA, respectively, as well as reviews the history, mechanisms of action, the therapeutic process used with psilocybin and MDMA, and any adverse physiological and psychological effects of both substances.