Violence and injuries are the second leading cause of death and lost disability-adjusted life years in South Africa. The overall injury death rate of 157.8 per 100,000 population is nearly twice the global average, and the rate of homicide of women by intimate partners is six times the global average. With a focus on homicide, and violence against women and children, we review the magnitude, contexts of occurrence, and patterns of violence, and refer to traffic-related and other unintentional injuries. The social dynamics that support violence are widespread poverty, unemployment, and income inequality; patriarchal notions of masculinity that valourise toughness, risk-taking, and defence of honour; exposure to abuse in childhood and weak parenting; access to firearms; widespread alcohol misuse; and weaknesses in the mechanisms of law enforcement. Although there have been advances in development of services for victims of violence, innovation from non-governmental organisations, and evidence from research, there has been a conspicuous absence of government stewardship and leadership. Successful prevention of violence and injury is contingent on identification by the government of violence as a strategic priority and development of an intersectoral plan based on empirically driven programmes and policies.