Metabolomics represents the global profiling of metabolites in a given biological system. It has been used to facilitate pharmaceutical discovery and development for over a decade. Advances in instrumentation have positioned capillary electrophoresis-mass spectrometry (CE-MS) as an important platform for both targeted and non-targeted metabolomics. In this mini-review covering the last five years, we focus on the latest development of CE-MS based metabolomics in (a) identification and validation of novel valuable therapeutic targets, (b) evaluation of drug efficacy, and (c) monitoring of drug unanticipated adverse effects. Some of the current issues and future directions of CE-MS metabolomics are also discussed in the end.