Treatment of chronic pain has created a “silent epidemic,” a term that describes the serious public health problem of the abuse of opioid painkillers and other prescription drugs. Conventional pharmacotherapy is limited by the loss of effectiveness in the long-term and by potentially lethal side effects. Efforts need to be focused on the development of nonpharmacological approaches. As significant progress is made in the viral vector technology, gene therapy involving recombinant viruses as vehicles may become a viable alternative for treatment of severe pain. Virus-based gene therapy has several advantages: (1) the transfer of a therapeutic gene to produce/release bioactive therapeutic molecules in a specific location in the nervous system thus minimizing the risks of off-target side effects, and (2) sustained long-term production of the therapeutic agent. This review compiles recently developed strategies for gene therapy targeting specific mechanisms of specific chronic pain conditions. A few successful studies on animal models of chronic pain have been translated to human clinical trials.