Microfluidic liquid chromatography is an attractive alternative to nano and micro capillary systems as the integrated nature of the systems simplifies fluidic connections, can provide minimal band broadening, and interface to mass spectrometry in a seamless fashion.However, there are a number of technical challenges in designing systems that achieve this potential and provide the performance of current capillary systems packed with sub-2 micron particles and operating at pressures up to 1000 bar or greater.This talk will describe some of the major advances we have made the past several years in materials fabrication, fluidic design and mass spectrometry interfacing that have resulted in high performing systems at chromatographic scales equivalent to a range of 75 to 300 micron ID.This design flexibility is useful for a number of life applications, including peptide mapping for biopharmaceutical analysis and global tryptic digests for proteomics, which will be used to illustrate system performance.