In the past 40 years, disordered mineral metabolism has been among the most intensely studied areas of nephrology. A June 2010 PubMed search for 'secondary hyperparathyroidism and kidney disease' yielded 5866 references. Among these are papers documenting the development and application of numerous therapeutic agents-including calcitriol, vitamin D analogs, phosphate binders, and cinacalcet-that remain in widespread use in the day-to-day management of dialysis patients worldwide. However, almost 6000 papers later, fundamental pathophysiological concepts remain unclear, particularly regarding the early pathogenesis of disordered mineral metabolism.