A number of studies have shown that underutilization of biospecimens from bioresources (biobanks and biorepositories) is a significant concern. In addition, biospecimen underutilization has been identified as an ethical as well as practical concern. The utilization of biospecimens is affected by many factors, including the establishment of a scientific need for the biospecimens, the design of the bioresource, strategic planning, biospecimen quality and fitness for purpose, informed consent considerations, access policies and procedures, and marketing. This article discusses the impact of these factors on biospecimen utilization and provides suggestions for how bioresources can optimize biospecimen utilization from their collections.