Alexander Randall described eight decades ago a heterogeneous nucleation process at the tip of the renal papillae giving birth to calcium oxalate stones. Kidney stones were for the first time described to originate from calcium phosphate plaques growing in the interstitial tissue, breaking the urothelium and then promoting calcium oxalate crystal aggregation at their contact. During the next decades, few studies were dedicated to these Randall’s plaques but the increasing incidence of calcium oxalate kidney stones, the development of endoscopic procedures allowing plaque visualization and series evidencing the high proportion of calcium oxalate stones generated on these plaques renewed interest in Randall’s plaque. Although some progress has been made during the past two decades, the origin of Randall’s plaques, their composition, their role in kidney stone epidemic, their specific affinity for some crystalline phases, and their potential deleterious effects on kidney tissues are among the challenges that lie ahead.