South Africa has one of the highest murder rates in the world and a female murder (femicide) rate that is five times the global average. In this chapter, the authors explore the unique features of femicide in South Africa from a historical and contemporary perspective and argue that the country presents a distinct epidemiology of female murder, which has more in common with profiles of fatal violence against women in countries in the global south than countries in the global north. From this, the chapter suggests the need to build more robust, regional-focused, evidence-based risk assessments and mitigation strategies that take into account localised contexts and conditions (including social, health and criminal justice systems) when trying to understand and disrupt fatal violence against women.