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SMA is an autosomal recessive disorder affecting motor neurons that is typically caused by homozygous whole\u2010gene deletions of <jats:italic>SMN1<\/jats:italic>. DMD is an X\u2010linked recessive muscle disease most often due to exon deletions, but also duplications and smaller sized variants within the <jats:italic>DMD<\/jats:italic> gene. Gene replacement therapy offers the opportunity to correct the underlying genetic defect by the introduction of a functional gene. We review the transformative work from clinical trials to United States Food and Drug Administration approval of onasemnogene abeparvovec\u2010xioi in SMA and its application in clinical practice and the early results of microdystrophin delivery in DMD. We also review the introduction of antisense oligonucleotides to alter pre\u2010messenger RNA splicing to promote exon inclusion (as in nusinersen in SMA) or exclusion (as in eteplirsen in DMD) into neuromuscular therapeutics. 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