The kidney has anatomic and physiologic features that prevent protein from reaching the urine. In disease processes, this natural mechanism is disrupted, causing protein to leak into the urine. Proteinuria can be used as a marker for disease and disease progression. The general anatomy of the glomerulus along with preliminary workup to evaluate disease based on history, physical and urinalysis results are reviewed in this article. Examples of commonly encountered diseases in the outpatient setting and relevance of proteinuria in chronic kidney disease along with general complications and treatments are also reviewed.