Trazodone is approved by the Food and Drug Administration (FDA) for the treatment of depression and anxiety in humans, it can perform these functions due to its selective serotonin receptor antagonism and reuptake inhibition properties. Trazodone has not been approved for animals by the FDA but it is legally prescribed by veterinarians as an offlabel drug for dogs and cats. This review describes trazodone's mechanism of action, pharmacokinetic properties and adverse effects and summarizes the benefits of trazodone for non-approved FDA indications to reduce anxiety, behavioral stress, sedation, pre-and post-operation stress. It also discusses its cardiac safety profile for dogs and cats. As few clinical trials have been conducted to evaluate trazodone's efficacy for treatment of the many behavioral and medical conditions in animals, large and randomized controlled clinical trials are still needed to confirm its efficacy in clinical practice.