It is imperative that primary care clinicians have a thorough understanding of insomnia, because they are often the first point of contact for patients who seek assistance when they have difficulty sleeping. Insomnia may appear with different presentations: sleep onset, sleep maintenances, sleep offset, nonrestorative sleep, or a combination of these symptoms. Untreated symptoms result in clinically significant distress or impairment in social, occupational, or other important areas of following-day functionality. Physicians, pharmacists, and other clinicians should be aware of the conditions that contribute to, are antecedent to, and associated with insomnia. These pathophysiological conditions include advanced age; female gender; respiratory, gastrointestinal, vascular, and rheumatologic pain syndromes; and other conditions such as depression and/or anxiety. Additional health factors contributing to insomnia include chronic pain, stressors, grief reaction, pharmacotherapeutic side effects, lifestyle contributors such as social/recreational drugs, phytopharmaceuticals, and ethanol use. The pharmacotherapy focus in this article is a modified-release formulation of the BZ1 (omega1) receptor agonist zolpidem, zolpidem extended-release. Pharmacokinetic, pharmacodynamic, and safety studies that compare 12.5 mg zolpidem extended-release (Ambien CRtrade markCIV) and 10 mg original zolpidem were initially conducted in healthy volunteers to assess the potential for an improved clinical profile. Zolpidem extended-release (12.5 mg and 6.25 mg extended-release dosage forms) is indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance. Zolpidem extended-release is devoid of any short-term use limitation and can be prescribed for the duration of medical necessity. The modified-release zolpidem is a two-layer tablet with a biphasic release profile, releasing the first layer immediately, whereas the second layer is released at a slower rate. Plasma concentrations are maintained for a longer period of time versus the immediate-release zolpidem formulation. Pharmacokinetic analysis has also demonstrated that the time to maximum concentration (tmax) and terminal elimination half-life (t1/2) of 12.5 mg zolpidem extended-release are similar to those of 10 mg zolpidem indicating a similar rapid onset of action and an elimination profile that reduced the risk of next-day decrements in performance. Zolpidem's CYP 450 hepatic metabolism uses as a substrate CYP3A4 (major) and 1A2, 2C9, 2C19, and 2D6 as minor pathways. Zolpidem extended-release dosage forms diminish sleep latency, number of awakenings, and wakefulness after sleep onset and augments total time asleep.