The prevalence of chronic kidney disease (CKD) has increased and will continue to increase in the United States and worldwide. This is alarming considering that CKD is an irreversible condition and patients who progress to chronic kidney failure have reduced quality of life and high mortality rates. As such, it is imperative to identify modifiable risk factors to develop strategies to slow CKD progression. One such factor is hyperuricemia. Recent observational studies have associated hyperuricemia with kidney disease. In addition, hyperuricemia is largely prevalent in patients with CKD. Data from experimental studies have shown several potential mechanisms by which hyperuricemia may contribute to the development and progression of CKD. In this article, we offer a critical review of the experimental evidence linking hyperuricemia to CKD, highlight gaps in our knowledge on the topic as it stands today, and review the observational and interventional studies that have examined the potential nephroprotective effect of decreasing uric acid levels in patients with CKD. Although uric acid also may be linked to cardiovascular disease and mortality in patients with CKD, this review focuses only on uric acid as a potential therapeutic target to prevent kidney disease onset and progression.