Chronic pain is a highly prevalent condition that impacts adversely on individual quality of life, imposes substantial costs on the healthcare system and a considerable burden on society. Advances in the understanding of pain mechanisms have opened the way for the development of new treatment strategies. The continuous delivery of short-lived potent bioactive molecules to sensory nerves, spinal cord or meninges--achieved by directed gene transfer--offers the possibility to selectively interrupt nociceptive neurotransmission or to interfere with the plastic changes in the nervous system underlying the development or persistence of chronic pain. In this review we describe advances in the use of non-viral and viral vector-based gene transfer for the treatment of pain, with a special focus on the use of recombinant non-replicating herpes simplex virus-based vectors and the prospects for clinical trials.