DNA is a fundamental building block for an individual’s entire genetic makeup. DNA is also a powerful tool when biological evidence from crime scenes is collected and stored properly; forensically valuable DNA can be found on evidence that may be decades old. This special report by the National Institute of Justice, Office of Justice Programs, U.S. Department of Justice is intended for use by law enforcement and other criminal justice professionals who have the responsibility for reviewing and investigating unsolved cases. Advancements in DNA technology and the success of DNA database systems have inspired law enforcement agencies to reevaluate cold cases for DNA evidence. The report is divided into four specific areas. The first reviews the long and short of DNA with special focus on DNA’s similarities to fingerprints and DNA technology advancements, such as PCR analysis, STR analysis, Mitochondrial DNA analysis, and Y-chromosome analysis. The report continues with the development, expansion, and limitations of DNA databases containing DNA profiles and their effectiveness in enhancing law enforcement’s ability to solve cold cases with DNA, specifically the Combined DNA Index System (CODIS). The third area discusses a broad range of considerations necessary before any DNA testing is actually attempted in older, unsolved cases and include: legal considerations, technological considerations, practical considerations, evidence considerations, victim and witness considerations, and resource issues. The final area addresses the identifying, analyzing, and prioritizing of cases.