Despite improved knowledge regarding disease causality, new drug targets, and enabling technologies, the attrition rate for compounds entering clinical trials has remained consistently high for several decades, with an average 90% failure rate. These failures are manifested in an inability to reproduce efficacy findings from animal models in humans and/or the occurrence of unexpected safety issues, and reflect failures in T1 translation. Similarly, an inability to sequentially demonstrate compound efficacy and safety in Phase IIa, IIb, and III clinical trials represents failures in T2 translation. Accordingly, T1 and T2 translation are colloquially termed 'valleys of death'. Since T2 translation dealt almost exclusively with clinical trials, T3 and T4 translational steps were added, with the former focused on facilitating interactions between laboratoryand population-based research and the latter on 'real world' health outcomes. Factors that potentially lead to T1/T2 compound attrition include: the absence of biomarkers to allow compound effects to be consistently tracked through development; a lack of integration/'de-siloing' of the diverse discipline-based and technical skill sets involved in drug discovery; the industrialization of drug discovery, which via volume-based goals often results in quantity being prioritized over quality; inadequate project governance and strategic oversight; and flawed decision making based on unreliable/irreproducible or incomplete data. A variety of initiatives have addressed this problem, including the NIH National Center for Advancing Translational Sciences (NCATS), which has focused on bringing an unbiased academic perspective to translation, to potentially revitalize the process. This commentary provides an overview of the basic concepts involved in translation, along with suggested changes in the conduct of biomedical research to avoid valleys of death, including the use of Translational Scoring as a tool to avoid translational attrition and the impact of the FDA Accelerated Approval Pathway in lowering the hurdle for drug approval.