The prevalence of hepatitis B virus (HBV) infections is a worldwide issue that can lead to both acute and chronic complications with increased morbidity and mortality in affected individuals. Current methods of preventing HBV infections primarily include building patient immunity through administration of hepatitis B vaccinations starting at birth. Certain at-risk individuals, including those with occupational exposure to pathogenic bodily fluids, those who are sexually active or intravenous drug users, are recommended to receive some form of hepatitis B vaccination. The current standard of hepatitis B vaccination in the United States is the Engerix-B vaccine, which consists of a three-dose regimen over a 6-month time period. A new hepatitis B vaccine, Heplisav-B, has been approved for adults in the United States and requires only two doses over 1 month. The unique dosing schedule of Heplisav-B provides the potential for increasing patient compliance and therefore can aid in the effort toward protecting individuals from developing an HBV infection. Results from clinical trials showed that Heplisav-B compared favorably with Engerix-B in safety and efficacy profiles. This paper provides a review of the pharmacology, safety, clinical trials and indications for use for the Heplisav-B vaccine in the United States.