The aim of gene therapy is to modify the genetic material of living cells to achieve therapeutic benefit. Gene therapy involves the insertion of a functional gene into a cell, to replace an absent or defective gene, or to fight an infectious agent or a tumour. At present, a wide variety of somatic tissues are being explored for the introduction of foreign genes with a view towards treatment. A prime requirement for successful gene therapy is the sustained expression of the therapeutic gene without any adverse effect on the recipient. A highly desirable vector would be generated at high titres, integrate into target cells (including non-dividing cells) and have little or no associated immune reactions. Lentiviruses have the ability to infect dividing and non-dividing cells and, therefore, constitute ideal candidates for development of vectors for gene therapy. This review presents a description of available lentiviral vectors, including vector design, applications to disease treatment and safety considerations. In addition, general aspects of the biology of lentiviruses with relevance to vector development will be discussed. Recent investigations have revealed that foamy viruses, another group of retroviruses, are also capable of infecting non-dividing cells. Thus, foamy virus vectors are actively being developed in parallel to lentivirus vectors. This review will also include various aspects of the biology of foamy viruses with relevance to vector development.