This chapter explores the persistent challenge of the “Valley of Death” in biotechnologyBiotechnology innovation—the gap between early-stage research and successful commercialization. It examines why many promising biotechnological advances, despite substantial scientific breakthroughs, fail to achieve widespread market adoption or societal impact. The chapter utilizes established readiness frameworks—Technology Readiness LevelsReadiness levels (TRL), Manufacturing Readiness Levels (MRL), and Integration Readiness LevelsReadiness levels (IRL)—to analyze this problem. It highlights the unique factors that make the Valley of Death particularly severe for biotechnologyBiotechnology, including inherent biological variability and unpredictability during scale-up, the capital-intensive infrastructure required for biomanufacturing, significant regulatory uncertainty, fragmented funding ecosystems, risk-averse private capital, and the absence of a clear Regulatory Readiness Level (RRL) framework. The chapter then suggests ways to bridge this gap, such as developing biotech-specific readiness frameworks like RRLs, expanding pilot-scale infrastructure through biofoundries, reforming investment models, and leveraging government as an early customer to de-risk innovation. Addressing these systemic challenges is presented as crucial for realizing biotechnology’s full economic, environmental, and societal benefits.