Classical physiological studies using electrophysiological, biophysical, biochemical, and molecular techniques have created a detailed picture of molecular transport, bioenergetics, contractility and movement, and growth, as well as the regulation of these processes by external stimuli in cells and organisms. Newer systems biology approaches are beginning to provide deeper and broader understanding of these complex biological processes and their dynamic responses to a variety of environmental cues. In the past decade, advances in mass spectrometry-based proteomic technologies have provided invaluable tools to further elucidate these complex cellular processes, thereby confirming, complementing, and advancing common views of physiology. As one notable example, the application of proteomics to study the regulation of kidney function has yielded novel insights into the chemical and physical processes that tightly control body fluids, electrolytes, and metabolites to provide optimal microenvironments for various cellular and organ functions. Here, we systematically review, summarize, and discuss the most significant key findings from functional proteomic studies in renal epithelial physiology. We also identify further improvements in technological and bioinformatics methods that will be essential to advance precision medicine in nephrology.