Proteinuria is a common finding in primary care practice. Most adolescents who are diagnosed with proteinuria through screening urinalysis do not have renal disease, and the proteinuria will usually resolve on repeat testing. In contrast, proteinuria is suggestive of kidney disease in patients with diabetes mellitus, hypertension, primary renal disease, or other systemic illnesses. Quantification of proteinuria can be used longitudinally to monitor therapeutic effects of treatment of the underlying disease. Given the multitude of clinical settings in which proteinuria can occur, we suggest an algorithm that may help clinicians differentiate between benign and serious etiologies of proteinuria.