Progressive multifocal leukoencephalopathy (PML) is severe, rare disease of the brain. It is caused by polyoma virus JVC that belongs to the Papovaviridae family. Mechanism of the disease is the involvement and the impairment of T-helper cells. Numerous focal plaques of demyelinisation develop in central nervous system white matter after the reactivation of JVC virus. The most cases of PML occurred among patients infected by HIV or with lymphoproliferative diseases. Lastly some reports of PML development during biological therapy of SM and Crohn disease were reported. PML was unexpectedly observed in 3 among 3000 cases treated with natalizumab the drug blocking alpha4beta1 integrins in bone marrow and spleen. Natalizumab was withdrawn from clinical studies in early 2005. Biological drugs cause deep perturbation in the immune system. Administration of the drug can be accompanied with PML or similar, severe infections. A high state of vigilance will be required during the treatment by these agents.