The African buffalo is one of the best-researched of all ungulate species even though it must give way to some North American deer species, an elephant-seal species and the red deer. The African buffalo had some monographs dedicated to it, but much new research has been carried out on the species since that time, which is brought up to date in the present volume. This allowed us to make an inventory of what we do not know yet about this important species. For that purpose, we made an inventory of research topics, or questions tabulated under three different knowledge domains, (i) ‘known unknowns’, (ii) ‘unknown unknowns’ and (iii) ‘unknown knowns’. The ‘known unknowns’ we categorized as those research questions sitting as it were in the backs of the minds of the current suite of African buffalo specialist; our inventory yielded 37 research issues. The ‘unknown knowns’, we portrayed as evidence-based scientific knowledge on buffalo that a current generation of scientists appear to have forgotten. This proved difficult, but three topics were identified. Here we also draw attention to the fact that modern scientists appear to ignore francophone literature, which is rather unfortunate as West and Central Africa are to a large extent francophone. Not using this repository of information may lead to knowledge decay. Finally, we share thoughts on the ‘unknown unknowns’, which we described as ‘knowledge once we have it will upset our present thinking, perhaps about African buffalo, perhaps on ecology evolution, or on aspects of the veterinary sciences’. Under this category, we touched on 15 issues, but perhaps our imagination was too limited. So, we share in total some 60-odd questions and ideas, and we hope that at least some of these questions or ideas will kindle someone’s imagination and drive to bring knowledge on this great species further.