Sample preparation for headspace analysis of volatile organic compounds (VOCs) by gas chromatography (GC) is well understood. Newer direct‑injection mass spectrometry (DIMS) techniques have found application in headspace analysis, but with some necessary modifications due to (i) the removal of the chromatographic column, and (ii) the soft chemical ionization that is used in these techniques. These factors place important constraints on the total load of VOCs—whether of solvent(s), analytes, or other VOCs in the matrix. This article summarizes the basic differences between DIMS and GC approaches, and describes the strategies by which headspace-DIMS can be successfully adopted.