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We will report advances in high-efficiency nanoscale capillary HPLC (including constant pressure, constant flow, fully automated multiple-column and 2D systems) coupled with high performance Fourier transform mass spectrometry (FTMS) for proteomic and degradomic analyses.These advances enabled: 1) confident identification (1% false discovery rate) of ~ 12,000 peptides (corresponding to ~2,000 proteins) using 50 μm i.d.× 200 cm long column in a single LC-tandem mass spectrometry analysis1; 2) limit of detection in the zeptomole range with 15 μm i.d.column2; and 3) ultrafast LC-MS analysis (5 min gradient) still resulting in ~2,000 confident peptide (and corresponding 600 protein) identifications 3.