Many modern analytical instruments, such as mass spectrometry, have been developed to provide insight into the biochemical content of many different biological sample types. Typically these instruments are large bench-top machines that have very high sensitivity and specificity for the compounds they detect. However, these instruments are not mobile or autonomous, and they require highly trained personnel to operate. There have been many developments in the area of miniature chemical sensors that can maintain performance levels observed in large traditional bio-analytical instruments, but are low-power and potentially mobile and autonomous in function. Miniature differential mobility spectrometry (DMS) is a small instrument that can potentially be used in point-of-care diagnostic applications. This chapter will review the significant advances in this emerging research area, and provide insight as to how these systems could be further improved and adapted for use in autonomous health monitoring and sensing systems.