The appearance of albumin in the urine has long been recognized as a cardinal feature of kidney disease and more recently has been shown to also be an independent cardiovascular risk factor associated with insulin resistance. Recent studies on rare human genetic variants, targeted gene disruption in mouse models and cultured glomerular cells in vitro have dramatically improved our understanding of the cellular and molecular basis of albuminuria. This review aims to summarize the current state of knowledge, to illustrate known mechanisms of proteinuria in disease states and to suggest a possible explanation for the link between albuminuria and insulin resistance.