Rapidly progressive renal failure (RPRF) is an initial clinical diagnosis in patients who present with progressive renal impairment of short duration. The underlying etiology may be a primary renal disease or a systemic disorder. Important differential diagnoses include vasculitis (systemic or renal-limited), systemic lupus erythematosus, multiple myeloma, thrombotic microangiopathy and acute interstitial nephritis. Good history taking, clinical examination and relevant investigations including serology and ultimately kidney biopsy are helpful in clinching the diagnosis. Early definitive diagnosis of RPRF is essential to reverse the otherwise relentless progression to end-stage kidney disease.