Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis of medium-sized vessels with clinical manifestations resulting from ischemia and infarction of affected tissues and organs. Although the cause of most cases of PAN and the related disorder microscopic polyangiitis (MPA) remains largely unknown, there has been significant progress in understanding the pathogenesis of vascular inflammation. The diagnostic approach to PAN and MPA should be individualized and based on specific organ involvement. Because no test or clinical finding reliably indicates the presence or absence of PAN or MPA, diagnosis requires integration of clinical findings, angiography, and biopsy data.