This article reviews the latest methodological and instrumental improvements for enhancing sensitivity and resolution in MEKC-based determinations. On-line sample concentration (stacking, sweeping and combination of two protocols) and other on-capillary approaches such as in-capillary derivatization and the coupling of flow-injection systems with MEKC are the most relevant methodological approaches discussed for improving sensitivity. At the same time, changes in the BGE through the use of organic modifiers, ionic liquids, cations, CDs, non-ionic and zwitterionic surfactants, mixed micelles, vesicles and carbon nanostructures as well as 2-D CE and chemometric techniques for enhancing resolution are also considered in detail. Two instrumental approaches such as MS and LIF are also discussed, covering the proposals for overcoming the difficulties arising from the direct coupling of MEKC with MS and the excellent detection sensitivity achieved by LIF using the typical argon-ion laser and recent growth in the use of diode lasers as excitation sources. Some thoughts on potential future directions are also expressed.