This review provides an update on the research conducted on the fabrication and utilization of hypoxanthine (Hx) biosensors published over the past four decades. In particular, the review focuses on progress made in the development and use of Hx biosensors for the assessment of fish and meat quality which has dominated research in this area. The various fish and meat freshness indexes that have been proposed over this period are highlighted. Furthermore, recent developments and future advances in the use of screen-printed electrodes and nanomaterials for achieving improved performances for the reliable determination of Hx in fish and meat are discussed.