In recent years, South Africa has embarked on an ambitious endeavor to revitalize the nursing profession throughout the country. Nurses constitute the largest single group of health care providers in South Africa and ensuring that they are adequately educated and trained is critical as the country works to address the quadruple burden of disease resulting from the HIV and TB co-epidemic, high maternal and child mortality, high levels of violence and injuries, and an increasing prevalence of non-communicable diseases. As with the scale-up of HIV treatment, nurses will be central to increasing access to quality care as South Africa works to meet a complex matrix of public health challenges.