Viral gene therapy vectors promise new opportunities for treatment of hitherto debilitating and life threatening illnesses. To enable early and rapid clinical evaluation of the therapeutic potential of the technology, the initial objectives of process development have so far largely concerned vector assembly, product quality and safety, and manufacturing consistency appropriate to modest scales. The first of such vectors are under test in clinical trials approved through the regulatory CTX/IND route and thus conform to the standards specified for purity and contaminant removal. Process optimisation, scale-up and operability have been of secondary concern and the establishment of a scientific basis for the mechanistic development of future vector manufacturing processes has yet to be seriously addressed. This review considers the manufacturing demands of retroviral vectors and the candidate separation technologies which could facilitate preparation of clinical grade materials. Note is made that the practising community appears to place implicit confidence in the capability of conventional membranes and chromatographic supports developed for protein purification to perform adequately for large-scale purification of viruses. In particular, these are expected to deliver virus preparations to product standards currently required of therapeutic proteins. It is argued that the basis for this confidence may be ill-placed, since the physical and chemical characteristics of viral particles differ significantly from macromolecular proteins. The specific requirements for separation systems and materials for processing of retroviral vectors are considered, and specific routes to more efficient manufacturing processes are proposed.