Pain is a common complaint in patients with autosomal-dominant polycystic kidney disease, and a systematic approach is needed to differentiate the etiology of the pain and define an approach to management. A thorough history is the best clue to the multifactorial causes of the pain, superimposed upon an understanding of the complex innervation network that supplies the kidneys. The appropriate use of diagnostic radiology (especially MRI) will assist in differentiating the mechanical low back pain caused by cyst enlargement, cyst rupture and cyst infection. Also, the increased incidence of uric acid nephrolithiasis as a factor in producing renal colic must be considered when evaluating acute pain in the population at risk. MRI is not a good technique to detect renal calculi, a frequent cause of pain in polycystic kidney disease. If stone disease is a possibility, then abdominal CT scan and/or ultrasound should be the method of radiologic investigation. Pain management is generally not approached in a systematic way in clinical practice because most physicians lack training in the principles of pain management. The first impulse to give narcotics for pain relief must be avoided. Since chronic pain cannot be "cured," an approach must include techniques that allow the patient to adapt to chronic pain so as to limit interference with their life style. A detailed stepwise approach for acute and chronic pain strategies for the patient with autosomal dominant polycystic kidney disease is outlined.