Although technical limitations exist with existing selective removal systems, very few products are available and no major clinical trials have demonstrated the superiority or equivalence of selective removal systems over plasma exchange. It is generally recognized that selective removal systems are preferable, and that selective macromolecule removal plasmapheresis systems are useful for autoimmune diseases or hyperlipidemia. In the treatment of a disease with a selective removal device, the disease pathogen should be identified and the efficacy of removal demonstrated. In general, for plasmapheresis applications, there is a need to better understand the pathophysiology of the disease states and to identify the pathogenic molecules. With such information, development of the optimal selective removal method will be possible. There is the need for clinical studies to compare selective removal and plasma exchange for specific disease states. Incentives for the development of improved selective removal technologies where cost effectiveness could be demonstrated should be encouraged.