Postweaning multisystemic wasting syndrome (PMWS) is a disease of pigs first recognised in North America in 1997 and subsequently reported worldwide that is caused by Porcine circovirus 2 (PCV2), a member of the family Circoviridae. The most consistent feature of PMWS is a generalized depletion of lymphocytes. Secondary infections with opportunistic organisms are common. There is evidence that the destruction of thymic lymphocytes has a central role in the pathogenesis of PMWS. Pigs with PMWS have altered cytokine responses to mitogens and recall antigens. It remains unknown what cells are primarily infected and are permissive for the replication of PCV2. Macrophages and dendritic cells commonly contain virus in their cytoplasm but may not be the primary source of the large amounts of virus found in tissues of diseased pigs. There is evidence that PCV2, like mammalian parvoviruses, requires cells in the S phase of the cell cycle for replication. It has been difficult to reproduce PMWS experimentally although some protocols have been developed which involve antigenic stimulation with other agents that presumably increase the number of permissive cells entering S phase of the cell cycle. In addition to reviewing the literature attempts are made to identify key unresolved areas that should be the focus of future research.