Differentiation of enantiomers remains one of the most attractive and important research areas in analytical chemistry due to its impact on pharmaceutical, chemical, biotechnology, and food industries. For a long time chiral separation techniques, such as high performance liquid chromatography (HPLC), gas chromatography (GC), and capillary electrophoresis (CE), have represented the gold standard for the separation and determination of enantiomers. These techniques, besides being time consuming and expensive, are also not suitable for real time analysis. Therefore, the development of fast and reliable chiral sensors remains a challenge to achieve on-line analysis of enantiomers in both gas and liquid samples. The scope of this chapter is to provide an overview on the basic functioning principles, as well as on the performance level, of solid-state sensing devices for enantiomers differentiation. Particular attention is paid to work providing a set of analytical figures of merit (sensitivity, repeatability, reproducibility, limit-of-detection, etc.) as well as to studies involving miniaturized (or miniaturizable) analytical devices that can deliver real-time, on-line, and label-free information on chiral compounds.