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Gene replacement therapies (GRTs) are increasingly expected to reach the market. Current healthcare systems are struggling to fund such valuable, costly therapies. GRTs are highly valuable as they extend life through sustained, long-term efficacy or by saving on the costs of a current high-cost standard of care. Some payers have implemented payment models, which do not address the budget impact on the year of acquisition or administration of costly GRTs. This study aims to (1) introduce amortization as an accounting tool within the context of healthcare, specifically for GRTs, (2) present a systematic literature review (SLR) on the amortization or depreciation of pharmaceuticals and medical devices, (3) assess the rationale and feasibility as well as the pros and cons of the amortization of GRTs, and (4) provide recommendations for future steps for the introduction of amortization for GRTs. The limited literature, identified in the SLR, has proposed amortization as a solution for costly, highly valuable GRT funding, but did not fully investigate and detail amortization and its feasibility. This paper further details and illustrates amortization as a promising method for these GRTs by facilitating market and patient access. Current accounting principles and guidelines must evolve to apply amortization to GRTs.