The show follows the cases of the Crime Scene Investigation division of the Las Vegas Police Department, usually referred to by officers as the "Las Vegas Crime Lab". Anthony E. Zuiker chose to set the series in Las Vegas because—as mentioned in the pilot —that city's crime lab is the second most active in the United States, after the Federal Bureau of Investigation lab in Quantico, Virginia.^[12] The division solves crimes almost entirely through forensics evidence, which may or may not come to conclusion of a murder or accidental death. The bizarre conclusions of these cases often force one to question morals, beliefs and human nature in general.

In reality, the crime lab and police department are the "Las Vegas Metropolitan Police Department", referred to locally as "Las Vegas Metro" or just "Metro". Zuiker has chosen not to use the proper "Metro" in the series.