Nigeria and South Africa account for about a third of Africa’s economic might, and have led much of its conflict management initiatives over the last two decades and a half. Both account for at least 60 per cent of the economy of their respective sub-regions in West and Southern Africa. The success of political and economic integration in Africa thus rests heavily on the shoulders of these two regional powers who have both collaborated and competed with each other in a complex relationship that is Africa’s most indispensable. Nigeria remains among South Africa’s largest trading partners in Africa, while both countries have cooperated in building the institutions of the African Union (AU). Both countries have also had a tremendous cultural impact on the continent in terms of Nollywood movies and the expansion of South Africa’s corporate sector into Africa. This lecture assesses Nigeria/South Africa relations in the areas of politics, economics, and culture within the context of rivalries and hegemony. Biographical profiles are also provided of seven important figures from both countries: Nelson Mandela, Sani Abacha, Thabo Mbeki, Olusegun Obasanjo, Nkosazana Dlamini-Zuma, Adebayo Adedeji, and Ngozi Okonjo-Iweala.