Ideally, gene therapies address the root causes of disease with a single curative dose. If they can replace a lifetime of expensive maintenance treatments this may lead to cost savings in the long run. Yet, the high upfront costs and uncertainty surrounding long-term efficacy and adverse events have caused payer push-back. Payer concerns are further exacerbated due to there being hundreds of gene therapies in the pipeline, across a wide range of therapeutic categories, from sickle cell anemia to HIV. Should many of these gene therapies be approved in the coming decade the budgetary impact burden on payers could become overwhelming.