INTRODUCTION: The National Institute for Health and Care Excellence (NICE) in England has appraised three treatments for spinal muscular atrophy (SMA), namely, nusinersen, onasemnogene abeparvovec, and risdiplam. As rare disease treatments (RDTs) commonly face challenges in health technology assessment (HTA) processes due to their clinical and economic uncertainties, an in-depth review of these appraisals is useful to enable a deeper understanding of economic modeling considerations for SMA. AREAS COVERED: This review is a detailed analysis of NICE appraisals for SMA and aims to compare the economic modeling evidence from the three RDTs. This is done by examining differences and similarities and by discussing critical outstanding issues across the economic evaluations of the appraisals. EXPERT OPINION: This article aims to contribute to the development of evidence that can be used as guidance to inform resource allocation decisions for RDTs for SMA, but also to be a resource about approaches for the generation, analysis and interpretation of economic modeling evidence for RDTs more broadly.