The fact that a Raman spectrum may be considered the fingerprint of an interrogated target by providing specific information on the particular chemical structures of the molecules present, has boosted the use of Raman spectroscopy for explosives detection in homeland and security applications. Also, the possibility of direct and distant access to suspect targets by stand-off Raman measurements makes this analytical technique a valuable tool in operational scenarios for security forces. The modest detection power as a result of the well-known, inherently low efficiency of the Raman scattering requires a careful evaluation of the experimental parameters governing the analytical response of this technique, particularly in respect to the amenable distance to target, the data acquisition speed, and the sources of uncertainty in any given measurement. The present paper highlights the importance of adequate instrumental parameters of the sensor according to the operational scenario when analyzing unknown targets. Raman fingerprints collected from a wide range of high explosives and associated compounds under different analysis conditions and operational scenarios have been evaluated in terms of signal strength, signal-to-noise ratio, analytical sensitivity, and signal stability. Copyright © 2012 John Wiley & Sons, Ltd.