Chronic kidney disease mineral-bone disorder (CKD-MBD) is a systemic disorder of abnormal serum levels of mineral-related biochemistries, abnormal bone, and extraskeletal calcification. Although we have gained understanding on how these components are interrelated, our therapeutic tools remain focused on only one aspect of CKD-MBD at a time. However, the management of these disorders is also interrelated; treatments may help one aspect of the disorder but cause or accelerate another. As such, management remains a major challenge to nephrologists and requires balancing risk and benefit of the various available therapies. Our challenge for the decade ahead is to determine which combinations of therapy can be used safely together to prevent morbidity and mortality in CKD. Furthermore, the pathophysiology that sets these events into motion begins well before the onset of ESRD. Future therapies and guidelines should, therefore, also emphasize the need for earlier detection and management of CKD, shaped by the results of valid clinical trials.