Trazodone is an antidepressant that is FDA-approved for the treatment of depression. It has been used by mental health and primary care providers for the treatment of multiple psychiatric and medical conditions. This review describes trazodone mechanism of action, formulation, dosage and adverse effects and then summarizes the beneficial effects of trazodone in the treatment of various psychiatric and medical conditions such as major depression, as well non-approved FDA indications such as insomnia, anxiety disorders, posttraumatic stress disorder, obsessive compulsive disorder, feeding and eating disorders, substance use disorders, behavioral disturbances associated with cognitive dysfunction, sexual dysfunction, certain pain conditions, and rehabilitation after acute ischemic stroke. Despite trazodone's favorable effects in the treatment of FDA-unapproved psychiatric and medical conditions, large, randomized controlled clinical trials are still needed to confirm its efficacy in the treatment of the multiple conditions for which it is often used in clinical practice.