This section is comprised of several units or squads that are staffed by specially-trained investigators. These units include:
- Cold Case Squad
- Drug Control Unit
- Evidence Detection Unit
- Family Services Unit
- Information & Analysis Unit
- Major Crimes Unit
- Missing Persons Unit
- Property Unit
- Special Investigations Squad
- Tech Crimes Squad
- Victims Assistance Unit
They are responsible for the investigation of major crimes ranging from burglary to homicide. Among their achievements are the conviction of Delaware's first serial killer, Stephen Pennell, and the apprehension of Delaware's first serial rapists, Michael Siple and Kevin Howard.