The characteristics of lentiviral vectors (stable integration in non-dividing and dividing cells, long-term expression of the transgene, absence of immune response) make them ideal gene transfer vehicula for future gene therapy. However, the most potent lentiviral vectors are derived from highly pathogenic human viruses, such as HIV. We describe how the field has engineered lentivectors with increasing biosafety both for the lab worker and for the patient. The risk associated with state-of-the-art lentivectors is therefore minimal, although a psychological barrier to use these vectors in the clinic may still have to be overcome. Due to their increased performance, care should be taken to avoid accidental transduction of the lab worker with potential hazardous genes. The precautions which have to be taken are described in detail.