The pathophysiology of disease in patients with paroxysmal nocturnal hemoglobinuria (PNH). Bone marrow failure and the occurrence of PNH blood cells are the two major components in the pathophysiology of PNH and explain the major clinical symptoms of patients with this disease, which are pancytopenia, hemolysis and thrombosis (see also text). The demonstration of blood cells deficient in GPI-linked proteins is sufficient for the diagnosis of the disease. Immune suppressive treatment improves bone marrow failure but does not influence the existence of PNH cells, whereas inhibition of intravascular hemolysis improves hemolysis-associated symptoms, but has no effect on bone marrow failure or on extravascular hemolysis. The increased understanding of the pathophysiology has greatly improved diagnosis and treatment of patients with this disease. However, a few critical “?” remain that need to be solved in order to fully cure the disease.