Insomnia remains a common clinical challenge for which a wide variety of substances and medications have been tried by individuals and recommended by health professionals. This chapter reviews the diagnosis of insomnia disorder and guidelines regarding the use of hypnotic medications. Four broad categories of insomnia pharmacotherapy are discussed: (1) Food and Drug Administration (FDA)-approved medications indicated for insomnia treatment, (2) FDA-approved medications indicated for alternate disorders but prescribed “off label” specifically for insomnia symptoms, (3) over-the-counter (OTC) antihistamine sleep aids, and (4) dietary supplement sleep aids. Key pharmacodynamic and pharmacokinetic properties of medications commonly prescribed for insomnia are reviewed. The chapter concludes with discussions of the basic elements of clinical trial investigations for insomnia medications and a review of investigational compounds and pharmacological strategies for possible future hypnotic medications.