In this work, I present the development and improvement of capillary electrophoresis (CE) methods and instrumentation. Included are advancements made for two-dimensional CE separations, the development and characterization of an online SERS detector for CE, an automated fraction collector for CE separations, a current sinking power supply for electrospray ionization mass spectrometry that is used with a CE instrument, and the development of an instrument and method for high through-put aptamer generation termed 2D-CE-SELEX.