Proliferation of chemical and explosive threats as well as illicit drugs continues to be an escalating danger to civilian and military personnel. Conventional means of detecting and identifying hazardous materials often require the use of reagents and/or physical sampling, which is a time-consuming, costly and often dangerous process. Stand-off detection allows the operator to detect threat residues from a safer distance minimizing danger to people and equipment. Current fielded technologies for standoff detection of chemical and explosive threats are challenged by low area search rates, poor targeting efficiency, lack of sensitivity and specificity or use of costly and potentially unsafe equipment such as lasers. A demand exists for stand-off systems that are fast, safe, reliable and user-friendly. To address this need, ChemImage Sensor Systems™ (CISS) has developed reagent-less, non-contact, non-destructive sensors for the real-time detection of hazardous materials based on widefield shortwave infrared (SWIR) and Raman hyperspectral imaging (HSI). Hyperspectral imaging enables automated target detection displayed in the form of image making result analysis intuitive and user-friendly. Application of the CISS’ SWIR-HSI and Raman sensing technologies to Homeland Security and Law Enforcement for standoff detection of homemade explosives and illicit drugs and their precursors in vehicle and personnel checkpoints is discussed. Sensing technologies include a portable, robot-mounted and standalone variants of the technology. Test data is shown that supports the use of SWIR and Raman HSI for explosive and drug screening at checkpoints as well as screening for explosives and drugs at suspected clandestine manufacturing facilities.