Granulomatosis with polyangiitis (GPA, formerly Wegener granulomatosis) is an ANCA-associated small-vessel vasculitis characterized by necrotizing granulomatous inflammation and vasculitis affecting the upper respiratory tract, lungs, and kidneys. Cytoplasmic ANCA (c-ANCA) directed against proteinase-3 (PR3) activates neutrophils, causing them to adhere to endothelial cells, degranulate, and release reactive oxygen species and proteolytic enzymes that damage vessel walls. The classic triad includes upper airway disease (sinusitis, saddle-nose deformity from nasal cartilage destruction, subglottic stenosis), pulmonary involvement (nodules, cavitary lesions, diffuse alveolar hemorrhage), and glomerulonephritis (rapidly progressive with crescent formation). The nurse assesses for signs of active vasculitis (epistaxis, hemoptysis, hematuria, skin lesions), monitors renal function and urinalysis, monitors c-ANCA/PR3 levels as markers of disease activity, administers prescribed remission induction therapy (rituximab or cyclophosphamide with corticosteroids), monitors for immunosuppression complications (infection, cytopenias), and assesses for treatment toxicity including cyclophosphamide-related hemorrhagic cystitis.