Alexander Randall described eight decades ago a heterogeneous nucleation process at the tip of 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 urothelium and then promoting calcium oxalate crystals 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 plaques 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 carried during the past two decades, the origin of Randall' plaques, their composition, their role in kidney stones epidemic, their specific affinity for some crystalline phases, and their potential deleterious effects in kidney tissues are among the challenges that lie ahead.