Advances in DNA sequencing technologies have resulted in an exponential increase in the identification of genetic variants, accompanied by the challenge of variant interpretation. Variants of uncertain significance (VUS) represent a significant problem in the diagnosis and associated patient care pathways for many conditions including inherited retinal degenerations (IRDs). The scale of the challenge is significant, with >40% of variants in genes associated with IRDs classified as VUS. Functional analyses can clarify the pathogenicity of variants, deepen our understanding of disease mechanisms, and importantly, impact patient care. This mini-review focuses on the application of functional analyses in the interpretation of variants in IRD genes: types of assays used and their utility in understanding pathogenicity.