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 tumor. At present, a 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 should be generated at high titers, stably integrate into target cells (including non-dividing cells), be nonpathogenic, and have little or no associated immune reaction. Lentiviruses have the ability to infect and stably integrate their genes into the genome of dividing and non-dividing cells and, therefore, constitute ideal candidates for development of vectors for gene therapy. This review presents a description of available lentivirus 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.