: Chronic insomnia, whether it is primary or in combination with another medical or psychiatric disorder, is a prevalent condition associated with significant morbidity, reduced productivity, increased risk of accidents, and poor quality of life. Pharmacologic and behavioral treatments have equivalent efficacy with each having its own advantages and limitations.: The purpose of this perspective is to delineate the limitations encountered in implementing cognitive behavioral therapy (CBT) and to review the pharmacological treatments designed to target the different phenotypes of insomnia. The discussions address how to choose the optimal medication or combination thereof based on patients’ characteristics, available medications, and the presence of comorbid conditions. Selective nonbenzodiazepine sedative ‘Z-drug’ hypnotics, melatonin receptor agonist-ramelteon, and low-dose doxepin are the agents of choice for treatment of primary and comorbid insomnia.: A pharmacological intervention should be offered if cognitive behavioral therapy for insomnia is not available or has failed to achieve its goals. Increasing evidence of the significant adverse consequences of long-term benzodiazepines should limit the prescription of these agents to specific conditions. Testing novel dosing regimens with a combination of hypnotic classes augmented with CBT deserve further investigation.