Hepatitis B virus (HBV) infection during the perinatal period remains a preventable cause of chronic liver disease in infants. Without appropriate post-exposure prophylaxis, up to 90% of infants infected at birth will develop chronic HBV infection, placing them at increased risk for cirrhosis and hepatocellular carcinoma later in life. This presentation reviews the epidemiology of perinatal HBV transmission, recommended screening and testing during pregnancy, and the critical role of timely newborn vaccination and hepatitis B immune globulin (HBIG) administration.