Duchenne muscular dystrophy (DMD) is the most common life-threatening childhood form of muscular dystrophy.1 It is an X-linked recessive disorder with an incidence estimated to be 1 in 3500 live male newborns. Mutations in the dystrophin gene,2 encoding a large (427-kDa) cytoskeletal protein found in skeletal and cardiac muscle, as well as smooth muscle, brain, and retina, cause DMD. The dystrophin gene is the largest gene identified to date,3 and because of its size, it is susceptible to a high sporadic mutation rate, ensuring that the disease can never be eliminated. It is estimated that 1 in 10 000 germ cells show de novo mutations, with some estimates as high as twice this number in certain populations.4 The consequences of the disease are debilitating, usually resulting in death in the early 20s in affected individuals; thus, medicine is challenged to find a treatment. Only corticosteroids have a salutary effect on DMD. Unequivocal proof was established in 1989 in a double-blind, randomized, controlled trial.5 The wide range of therapeutic prospects includes growth-modulating agents that increase muscle regeneration and delay muscle fibrosis,6,7 anti-inflammatory or second-messenger signal-modulating agents that affect immune responses,8- 10 powerful antisense oligonucletotides (2′-O-methyl phosphorothioate backbone or morpholinos) with exon skipping capacity,11,12 and agents designed to suppress stop codon mutations (aminoglycosides and other agents such as PTC-124 [PTC Therapeutics Inc, South Plainfield, New Jersey]).13,14 In this brief review, we examine the possibility of moving forward with gene therapy for muscular dystrophy, addressing topics that will be relevant to musculoskeletal disorders and gene therapy in general.