Our understanding of the mechanism responsible for secondary hyperparathyroidism (HPTH) has advanced significantly since the "trade-off" hypothesis was formulated. It appears that in early renal failure a deficit of calcitriol synthesis is an important factor. However, additional factors, such as a defect of the vitamin D receptor or the newly cloned calcium sensor receptor (BoPCaR1), may be present in the parathyroid cells. As renal failure progresses, the lack of calcitriol becomes more pronounced, inducing HPTH. With advanced chronic renal failure, hyperphosphatemia is an additional important factor in worsening HPTH. In addition, resistance of the parathyroids to calcitriol due to a reduced density of calcitriol receptors also may contribute to HPTH. Finally, uremia per se not only may cause a receptor abnormality in the parathyroid but at the level of the bone it may aggravate the impaired calcemic response to PTH. In conclusion, after reviewing the "trade-off" hypothesis, although some of the original concepts may have been simplistic, most of the factors postulated 30 years ago are still operative in the pathogenesis of secondary HPTH in renal failure.