Conventional methodology of protein mass spectrometry using collision induced dissociation (CID) has been widely adopted for confident identification and characterization of proteins in recent years. However, CID-based protein analysis works best with relatively short peptides and many important post translational modifications are not preserved during CID-based analyses. A new fragmentation method, electron transfer dissociation (ETD), has been developed recently and introduced to linear ion trap mass spectrometer. In ETD, peptide backbone is fragmented along pathways that are analogous to those observed in ECD. ETD has been reported to not only favor multiply charged, relatively large peptides, but also preserve post translational modifications. Thus, ETD is drawing more and more attention as mass spectrometry based methods for protein identification and analysis of post-translational modifications. However, current experimental strategies, which perfectly match CID-based analysis, are not optimized for ETD. This lack of efficient experimental strategies that enhance ETD-based analysis could significantly limit the benefits which ETD can provide for the analysis of proteins.