Numerous epidemiological studies conducted in the general population indicate that hyperuricemia is associated with an increased risk of developing renal failure. Moreover, among those subjects who are already suffering from chronic kidney disease (CKD), hyperuricemia is associated with a more rapid progression of disease besides with an increased risk of mortality and cardiovascular events. However, to date, the causal role of hyperuricaemia in determining the onset and progression of cardiovascular and renal damage is not yet fully established. Therefore the indications for pharmacological treatment of hyperuricemia (and particulary of asymptomatic hyperuricemia) in patients with CKD are still assigned to the personal orientation of the physician. In order to produce an evidence-based clinical appraisal on this topic, we performed a comparative analysis that included all the prospective studies that have evaluated the impact of treatment with xanthine oxidase inhibithors (XOI) with respect to the onset and progression of CKD. Moreover, since in the past the treatment with XOI was associated with a high risk of toxicity in patients with impaired renal function, we analyzed the toxicity of these drugs for various degrees of renal function impairment summarizing indications, contraindications and recommended doses in patients affected by CKD. In the end, as conclusion of our analysis, we propose an algorithm aimed at guiding the clinical decisions about the treatment of hyperuricemia in patients with CKD.