AHRI’s vision is optimal health and well-being of under-resourced populations. We conduct research on important, intractable and intersecting health problems which impact well-being and mortality in South Africa and globally. The highest prevalence of HIV and TB, globally, is in our province; our research on these infections will therefore continue, with new strategic directions. We will introduce research on emerging and neglected infections, building on extraordinary impact of our Covid-19 science. We will build a new research programme in adolescent common mental health disorders, which is a very significant local – and global – health challenge. AHRI is uniquely placed to address these challenges: we focus on research questions for which we have a competitive advantage and exploit our integrated research value chain of basic, translational, clinical, population and social sciences. We will introduce innovation in all these areas, while fostering a research culture of well-being and scientific success. We regard training of the next generation of African scientists as a priority. We cannot achieve success alone – we will nurture academic partnerships and optimise public engagement, particularly with our research communities. Our ultimate goal is impact on scientific knowledge, practice and policy, in South Africa and beyond.