Mass spectrometry has been the “gold standard” for drugs of abuse (DoA) analysis for many decades because of the selectivity and sensitivity it affords. Recent progress in all aspects of mass spectrometry has seen significant developments in the field of DoA analysis. Mass spectrometry is particularly well suited to address the rapidly proliferating number of very high potency, novel psychoactive substances that are causing an alarming number of fatalities worldwide. This review surveys advancements in the areas of sample preparation, gas and liquid chromatography‐mass spectrometry, as well as the rapidly emerging field of ambient ionization mass spectrometry. We have predominantly targeted literature progress over the past ten years and present our outlook for the future. © 2020 Periodicals, Inc. Mass Spec Rev