South Africa has much in common with Eastern Europe and Russia in that the reforms of the early 1990s opened markets to those previously excluded. These adjustments in the context of geopolitics, globalization, financial instability and climate change create special problems for country innovation systems. This contribution unpacks the forces in play and provides an overview of the state of South Africa’s modest-sized innovation system that supports her as ‘The Gateway to Africa’ and partner among the BRICS. Resource path dependence remains, endogenous factors include labour militancy, unstable power supply and low private sector confidence. STI policy has brought some coherence to the complexity by promoting big science and basic research. STI indicators are tabulated and system strengths are identified. Innovation actors have risen to the challenge through a number of open innovation projects that include organised labour and that are designed to address efficiency and effectiveness. The private sector, as in the past, is able to marshal forces where survival dictates.