Gene transfer vectors based on retroviruses including oncogenic retroviruses and lentiviruses provide effective means for the delivery, integration and expression of exogenous genes in mammalian cells. Lentiviral (LV) vectors provide attractive gene delivery vehicles in the context of non‐dividing cells. This review summarizes the different optimized LV genetic systems that have been developed to date. In all cases, the production of LV‐derived vectors consists of a genetically split gene expression design. The viral elements that are specifically required are (i) the LV packaging helper proteins consisting of at least the gag‐pol genes, (ii) the LV transfer vector RNA containing the transgene expression cassette, and (iii) an heterologous glycoprotein. While the genetic requirements and performances of the two former viral elements will be treated herein, the latter element relative to the envelope pseudotyping of LV vectors will not be further described (cf. review by Cosset in this issue). Copyright © 2004 John Wiley & Sons, Ltd.