Hydroxyzine is used primarily as an antihistamine for the treatment of itching, allergies, hyperalgesia, motion sickness-induced nausea, and insomnia, as well as notably for the treatment of mild anxiety. Even though it is an effective sedative, hypnotic, analgesic, and tranquilizer, it shares almost none of the abuse, dependence, addiction, and toxicity potential of other drugs used for the same range of therapeutic reasons.

Hydroxyzine is used with opioid analgesics to increase the pain-killing ability of a given dose of opioid, reduce the quantity needed to stop a given level of pain, and/or preempt some side effects of opioids like itching, nausea, and vomiting.

Hydroxyzine preparations usually require a doctor's prescription as do other potent antihistamines in many countries whereas some countries allow hydroxyzine and all or most other antihistamines to be sold over-the-counter. The drug is available in two formulations, the pamoate and the dihydrochloride or hydrochloride salts. Vistaril, Equipose, Masmoran, and Paxistil are preparations of the pamoate salt, while Atarax, Alamon, Aterax, Durrax, Tran-Q, Orgatrax, Quiess, and Tranquizine are of the hydrochloride salt.