Infection with the hepatitis B virus (HBV) is one of the leading global public health issues. Over 250 million people worldwide have chronic HBV infection, out of which roughly 65 million are women in their reproductive age. The most common route of passing the infection in areas of high endemicity is by mother-to-child transmission (MTCT). In children the infection may still occur despite adequate immunoprophylaxis, however, antiviral medication, such as Tenofovir disoproxil fumarate (TDF), may be helpful in reducing the risk of MTCT. A literature review was conducted concerning TDF’s role in preventing MTCT and its safety in pregnancy. Studies were identified by researching various databases up to 2020 for variations of the following sentence: “Tenofovir disoproxil fumarate and Lamivudine and Telbivudine and Entecavir and pregnancy and transmission and safety and HBV”. Prenatal and perinatal adequate management of maternal HBV infection is of utmost importance, with focus on prevention of MTCT as the key strategy to reduce the global HBV infection burden. This review discusses the most up-to-date evidence from a multidisciplinary perspective of using TDF to reduce MTCT of HBV infection as well as its safety profile for pregnant women.