The MALDI (matrix assisted laser desorption/ionization) technique, widely used to desorb and ionize large biomolecules, is applied here to small molecules having low vapor pressure, such as drugs and explosives. Furthermore, we report the coupling of the MALDI technique with a small, highly portable tiny-TOF (time-of-flight) mass spectrometer developed in our laboratories. This mass spectrometer is a low voltage coaxial reflectron design with a short flight tube that is specifically designed for low molecular weight substances. The reflectron is designed to operate in two different modes that provide an extremely powerful pseudo-tandem mass spectrometry capability that is crucial for field applications. Using this system we have measured mass spectral signatures for cocaine, heroine, and the explosive RDX in the sub-nanogram range. Also reported here are continued developments on advanced MALDI sampling technologies, sensitivity, and mass resolution enhancements of the tiny-TOF, further decreases in system size and weight, and concepts for field operational systems.