Urinalysis is an integral part of the assessment and management of individuals with kidney diseases. The finding of proteinuria in patients with kidney diseases is a poor prognostic sign for both for future renal function and cardiovascular disease. The role of proteinuria as an independent risk factor for renal function loss is now well recognized. The failing kidney is characterized histologically by tubulointerstitial inflammation, tubular cell apoptosis, tubular atrophy and fibrosis, and these changes correlate with the degree of proteinuria. Multiple clinical trials have indicated that antiproteinuric strategies are, in general, renoprotective. Such observations have led to the suggestion of a causal relationship between proteinuria and renal inflammation or scarring. Understanding the mechanisms underlying proteinuric nephropathy has attracted intense interest. It is now clear that the association between proteinuria and progression is causal and strong biological plausibility has been demonstrated. Targeting proteinuria is thus a rational target for clinical trial interventions.