Chronic kidney disease (CKD) is associated with increased mortality. Non-traditional risk factors, such as mineral metabolism disturbances, seem to contribute to the unexpected high mortality rate. A chronic kidney disease-mineral bone disorder (CKD-MBD) has recently been defined as a systemic disorder manifested by one or a combination of abnormalities in bone biopsy, laboratory parameters, and/or vascular or other soft tissue calcifications. Recent research developments and new available treatments have all contributed to move the former treatment paradigm beyond the control of PTH. Thus, despite much of the advice given by different societies being just opinion-based evidence, the effect of different drugs on laboratory parameters, vascular calcification (VC) or survival may steer the choice of specific treatments. Aluminum and calcium-based phosphorus binders have been associated either with metal toxicity or progression of VC. Sevelamer hydrochloride has been related to an attenuation of the progression of VC and it has also been associated with improved survival at least in certain subgroups of dialysis patients. Lanthanum carbonate decreases phosphorus levels but its impact on surrogate or hard outcomes is not known. Selective vitamin D-receptor activators may have differential effects on VC, are associated with a survival advantage and thereby may have a best-fitted profile for CKD patients. On the other hand, calcimimetics markedly help to achieve current guidelines and ongoing clinical trials are evaluating hard outcomes. It is likely that a regimen combining several drugs might improve individual results. However, the utility of any new approach to CKD-MBD will need to be evaluated in prospective trials including thorough pharmacoeconomic analysis.