Comprehensive two-dimensional liquid chromatography-capillary electrophoresis systems are summarized in this chapter. A variety of combinations of capillary electrophoresis and liquid chromatography modes as well as interfaces and detection technologies are discussed. A typical, comprehensive two-dimensional system coupled with reverse-phase liquid chromatography with fast capillary electrophoresis and hyphenated to mass spectrometry was demonstrated for proteomic analysis. A two-dimensional capillary electrophoresis system of coupling capillary sieving electrophoresis with micellar electrokinetic chromatography and its application in single cell analysis for protein expression profiling are presented.