The main scope of this review is to expose the main advances regarding recent research of psychedelic substances in the neurociences and their potential psychotherapeutic applications. Psilocybin, a 5-HT2A receptor agonist has been associated with reduced activity in the Default- Mode Network (commonly activated during introspection and self-reflection), enhanced access to biographical memories, positive emotional attentional bias and a reduction on anxiety and mood symptoms. The administration of 3,4-methylenedioxy-N- methylamphetamine (MDMA) could significantly aid the psychotherapeutic process in patients with Post-Traumatic Stress Disorder by strengthening the therapeutic alliance through the release of oxytocin, as well as facilitating emotional regulation from frontal areas to the amygdala during the recollection of traumatic memories. Furthermore, the administration of ayahuasca (an amazonic beverage containing dimethyltryptamine, which binds with the 5-HT2A receptor) and ketamine (a NMDA receptor agonist) in pilot studies has resulted in reduced problematic use of cocaine, heroine, alcohol and tobacco, as well as reported reduction in craving in addiction. While modern research with substances containing psychedelic properties is still young, initial findings suggest the need of expanding the number of studies in order to further clarify their potential risks, benefits and action mechanisms associated to their administration.