The majority of children diagnosed with “floppy infant syndrome” have autosomal recessive mutations in the SMN1 gene. AAV9-SMN1 replacement gene therapy performed early in life supports the survival and attainment of continuing motor milestones in these children. This was the first approved gene therapy for a disease of the brain or spinal cord and has transformed the treatment of what had been a uniformly fatal and tragic disease. Two other classes of treatment are also effective for SMA: antisense oligonucleotides, and oral medications that alter gene splicing patterns in the nervous system to raise compensatory levels of SMN2 genes. While some issues remain to be improved, the emergence of gene-targeted therapies for spinal muscular atrophy currently stands as one of the most important neurological therapeutic achievements of the twenty-first century.