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The Rutgers University Cell and DNA Repository (RUCDR), a not-for-profit unit of the Human Genetics Institute of New Jersey, has processed over 130,000 individual donor blood samples and has distributed over 400,000 DNA samples in the past nine years. The blood samples were directly obtained from several hundred collection sites in the United States and nearly all other parts of the world, mostly in support of investigator-initiated, NIH-funded projects directed toward the discovery of genes involved in complex diseases such as autism, alcoholism, bipolar disorder, diabetes, inflammatory bowel disease, schizophrenia, and substance abuse. During the most recent period, RUCDR has supplied large numbers of DNA samples for very high density SNP genotyping projects such as Genome Association Information Network (GAIN) and others. In the course of this work, RUCDR has introduced new technologies and automation as well as novel approaches toward quality assurance. We will review the critical steps that have produced this successful and cost-effective effort. As cell and DNA repositories will likely have increased utility in the future, we will present one view of the flexibility that will be necessary if we are to best serve our constituents—the individuals suffering from the complex diseases and the researchers attempting to find causes and treatments. As the RUCDR also serves the pharmaceutical and biotechnology industries, their needs will be contrasted with those of academic researchers.