An important consideration in the design of energetic materials is their sensitivity to decomposition induced by external stimuli. The practicality of any high energy material (HEM) is immediately constrained by its ability to be safely synthesized, formulated, and stored without significant risks of deflagration or detonation. In contrast to numerous studies that aim to predict the performance properties (detonation velocity, detonation pressure, etc.) of HEMs, analogous methods for the prediction of the sensitivity properties of HEMs (decomposition temperature (Tdec), impact sensitivity (IS), friction sensitivity, electric spark sensitivity) remain elusive. In the absence of robust predictive tools, the development of new energetic materials is often subject to time-consuming cycles of synthesis and characterization in which chemical insight is gained almost entirely through empirical trial-and-error. As such, the ability to precisely tune the properties of HEM candidates based on their chemical structures offers the potential to accelerate the development of new HEMs for military and civilian applications. Streamlined methods for the ab initio design of HEMs can also minimize hazardous experimental work associated with the preparation of these materials. Benefits of such methods extend further to the synthesis of fine chemicals, where energetic motifs such as nitrogen-containing heterocycles, azides, and nitro groups are commonly encountered in synthetic intermediates and in bioactive molecules. Therefore, understanding the decomposition thresholds of these motifs is also a component of improved safety in process development chemistry.