Paroxetine (Paxil) is classified as one of the serotonin reuptake inhibitors (SRIs) because of its potent inhibition of presynaptic serotonin (5-HT) uptake. It is also a relatively potent norepinephrine (NE) reuptake inhibitor, particularly at higher doses, leading some to argue for its inclusion in the growing class of acknowledged dual serotonin–norepinephrine reuptake inhibitors (SNRIs). Since its approval for the treatment of depression, paroxetine has been demonstrated to be effective and has been approved for a broad spectrum of anxiety disorders, including panic disorder, obsessive-compulsive disorder (OCD), social anxiety disorder, generalized anxiety disorder (GAD), and posttraumatic stress disorder (PTSD). Moreover, studies have demonstrated the efficacy of paroxetine in premenstrual dysphoric disorder (PMDD), postmenopausal hot flashes, and child and adolescent OCD and social anxiety disorder. Paroxetine is still one of the most prescribed antidepressant medications in the United States because of its proven efficacy, as demonstrated in randomized, double-blind clinical trials, and its much improved tolerability compared with tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). Although paroxetine shares many characteristics with other members of the SRI class, its unique pharmacological characteristics and clinical database are reviewed, with particular attention to the clinical setting.