The documentation of no other human disease threads as far into antiquity as that of urinary stones. However, despite this arcane history and the development of novel means of treating the condition, the basic mechanisms of stone formation and the identity of indicators of recurrence remain largely shrouded in uncertainty. This review is concerned with what scientific information is known about the cause and formation of calcium oxalate stones -the most common component of human uroliths. Stone pathogenesis can be broadly divided into two main processes: (1) nucleation of insoluble crystals in urine and (2) retention of those crystals within the urinary tract. The first section of the article presents the various factors that are known or surmised to influence the likelihood that crystals will nucleate within the renal collecting system, and these are considered from the perspective of both their relation to metabolic disorders and their usefulness as diagnostic and therapeutic indicators. A discussion of factors that may influence the probability that newly formed crystals will be retained within the nephron forms the second part of the review. In developing this more mechanistic aspect of the disease the epitaxy, matrix and inhibitor theories of stone formation are presented, with particular emphasis being placed on their relation to crystal nucleation, growth or aggregation, and experimental evidence both for and against the hypotheses are discussed.