Depression is one of the most disabling and prevalent mental disorders, which causes excessive feelings of sadness and despair. Unfortunately, there are a substantial number of patients that do not respond well to conventional interventions and new approaches are therefore needed. Recent studies have revealed that psilocybin can effectively reduce symptoms of depression and anxiety, particularly when combined with psychological support. It has been further suggested that psilocybin can reduce symptoms of alcohol abuse, cluster headaches and obsessive-compulsive disorder (OCD). Results have shown that psilocybin can give long-lasting beneficial changes in mood, behavior, values, and attitudes. Psilocybin enables creative thinking and increases emotional access, which seems suitable for therapeutic implications. Neuroimaging studies have shown that psilocybin alters similar neural networks to those in depressed patients, in particular: the medial prefrontal cortex, posterior cingulate cortex, and the amygdala. The mechanisms behind the clinical improvements are still poorly understood. Using psilocybin for clinical purposes is controversial since it is categorized as a Schedule I substance, although the drug is not physically addictive nor harmful and has low abuse potential. Recent studies have demonstrated that psilocybin has clinical potential and is safe to use in supervised settings.