In 2011, an estimated 34 million people globally were living with HIV, 2.5 million people became newly infected, and 1.7 million people died from AIDS-related illnesses. Although there has been a reduction of 700,000 new HIV cases since 2001, HIV/AIDS remains one of the leading causes of death globally. Since there is no known cure or vaccine currently present, preventing infection has become central to controlling the HIV/AIDS epidemic. With the United Nation's goal of "Getting to Zero" for the next generation, it may be warranted to review other successful global eradication strategies. The most well known global eradication may be the smallpox eradication program. Although both strategies aim to eradicate diseases, eradication of the HIV/AIDS epidemic has remained much more elusive. This paper will strive to demonstrate the similarities of the smallpox and HIV/AIDS global eradication programs, and the unique challenges HIV/AIDS poses for successful eradication. © 2013 Chung A, et al.