Prospective collection is a model through which biospecimens are provided for research. Using this model, biospecimens are collected based on real-time requests from the research community instead of being collected based on the prediction of future requests. We describe the lessons learned by two bioresources that have operated successfully using a prospective model for over three decades. Our goal is to improve other bioresources by increasing utilization of biospecimens that honor consented donors who provide biospecimens to the research community; this provides strong evidence of stewardship of the public trust. The operation of these sites requires flexibility, close communication, and cooperation with the investigator in developing a standard operating procedure (protocol) based on the investigator's needs described in their initial request. If practicable, almost any preparation can be provided, including fresh (nonfrozen) biospecimens and tissue blots. A quality management system includes rigorous quality control of the specific biospecimens provided to an investigator. The informatics approach focuses on the investigator, the investigator's request, and the biospecimens collected for the investigator; the informatics focus of classic biobanks is on the biospecimens collected to match expected future requests. These lessons have been incorporated into our current operations. Standard investigator agreements (e.g., indemnification and no unapproved biospecimen transfers to third parties) replace material transfer agreements. We have operated under the prospective model of the Cooperative Human Tissue Network (CHTN), which has been successful and has provided over 1.2 million biospecimens since it began in 1987. These tissues have supported over 4300 peer-reviewed scientific articles. Since 2012, about 1000 publications have indicated support by CHTN tissues; their average citation rate is 31 with an H factor of 61. Also, during this period, 114 patents cited the CHTN. We also describe disadvantages of prospective bioresources (e.g., inadequate distribution of rare tissues, biospecimens not immediately available, and delayed clinical outcomes).