CRISPR-based gene editing techniques hold the potential to revolutionize the development of gene-based therapies. However, the history of recently approved cell and gene therapies offers a cautionary tale that must be considered by pharmaceutical companies investing in CRISPR based therapies. Gene-based therapies already demonstrate promise for treating a wide range of diseases, yet they also present significant barriers to access, including high prices and reimbursement hurdles imposed by payers. Traditional health technology assessment methods create uncertainties when applied to these novel therapies and have given rise to new approaches to determining the value of these treatments. Payer coverage decisions are increasingly informed by considerations of the value of therapies for both the patient and the health care system, with value assessments combining an analysis of benefits, cost effectiveness, affordability, budget impacts, and lifetime time horizons. Advanced statistical techniques for survival modeling and multi-criteria decision analyses have been proposed for value determination, and a variety of innovative payment plans have been proposed to offset risks while maximizing benefits. Increased collaboration between drug developers, manufacturers, and payers at the pre-commercialization stage facilitates the development of meaningful, clinical endpoints and a viable market access strategy.