Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare acquired disease characterized by a clone of blood cells lacking glycosyl inostitol phosphatidyl (GPI) anchored proteins at the cell membrane. Deficiency of GPI-anchored complement inhibitors CD55 and CD59 on erythrocytes leads to intravascular hemolysis upon complement activation. Next to hemolysis, another prominent feature is a highly increased risk of thrombosis. Thrombosis in PNH results in high morbidity and mortality. Often, thrombosis occurs at unusual locations, with the Budd-Chiari syndrome being the most frequent manifestation. Primary prophylaxis with vitamin K antagonists (VKA) reduces the risk, but does not completely prevent thrombosis. Eculizumab, a monoclonal antibody to complement factor C5, effectively reduces intravascular hemolysis and also thrombotic risk. As such, eculizumab treatment has dramatically improved the prognosis of PNH. The mechanism of thrombosis in PNH is still unknown, but the highly beneficial effect of eculizumab on thrombotic risk suggests a major role for complement activation. Additionally, deficiency of GPI-anchored proteins involved in hemostasis may be implicated.