Urolithiasis has not been extensively researched in the African continent due to a general lack of facilities and resources. Consideration of the few published papers indicates that there are some regions where the occurrence of stones is extremely rare. South Africa is unique in two respects. Firstly, it has both stone-prone and stone-free population groups and secondly, it is an African country in which a fair amount of research has been conducted in this field. These studies have shown that routine urine parameters cannot explain stone rarity, but that structural differences of inhibitory urinary proteins appear to be important. Similarly, the studies have demonstrated that common dietary components cannot necessarily be correlated with urine composition, particularly oxaluria, nor can they necessarily explain stone rarity, but that the role of oxalate-degrading bacteria has the potential to offer explanatory insights. By investigating the factors influencing stone rarity, those affecting stone formation have been concomitantly scrutinized. As a result, it is suggested that a paradigm shift from a focus on pathology to one on physiology is needed in urolithiasis research in general.