In this article, the benefits of urinary proteomics in comparison with kidney biopsy are discussed. The majority of urinary proteins are generated by the kidney, hence the urinary proteome holds substantial information on the kidney, and assessment of the urinary proteome could be considered a ‘liquid biopsy’. The main question is how well the information contained in the urinary proteome can be assessed today, if it is ready to be routinely used, and what are the advantages and possible disadvantages in comparison with current standards. Since chronic kidney disease (CKD) is by far the largest area in nephrology based on the number of patients affected, the focus of this article is on CKD. Substantial progress was made in the last decade in urinary proteomics, and today we have comparable urinary proteome datasets of tens of thousands of subjects available. Clinical proteomics studies in CKD including close to, or even exceeding, 1000 subjects have recently been published, demonstrating a benefit over the current state-of-the-art in diagnosis and especially prognosis. The first large multicentric randomized controlled intervention trial aiming at preventing CKD by employing urinary proteomics-guided intervention has been initiated recently. These data provide ample evidence for the utility and value of urinary proteomics in nephrology. A further consideration is that the purpose of the biopsy, be it ‘liquid’ or ‘solid’, is to guide intervention. However, essentially all drug targets are proteins, not microscopic structures. Therefore, obtaining information on the proteome to guide intervention appears to be the most appropriate approach. Presenting more detailed evidence, I argue that urinary proteome analysis can, in most cases, be employed to guide therapeutic intervention, can be repeated multiple times as it is without any direct risk or discomfort and can be considered as a liquid biopsy.