As in the case of other heavy metals, a considerable body of evidence suggests that overexposure to uranium may cause pathological alterations to the kidneys in both humans and animals. In the present work, our aim was to analyze the available data from a critical perspective that should provide a view of the real danger of the nephrotoxicity of this metal for human beings. A further aim was to elaborate a comparative compilation of the renal pathophysiological data obtained in humans and experimental animals with a view to gaining more insight into our knowledge of the mechanisms of action and renal damage. Finally, we address the existing perspectives for the improvement of diagnostic methods and the treatment of intoxications by uranium, performing an integrated analysis of all these aspects.