AbstractThis review provides a broad overview of recent Fourier transform ion cyclotron resonance (FTICR) applications and technological developments relevant to the field of proteomics. Both the “bottom up” (peptide level) and “top down” (intact protein level) approaches are discussed and illustrated with examples. “Bottom up” topics include peptide fragmentation, the accurate mass and time (AMT) tag approach and dynamic range extension technology, aspects of quantitative proteomics measurements, post‐translational modifications, and developments in FTICR operation software focused on peptide and protein identification. Topics related to the “top down” approach include various aspects of high mass measurements, protein tandem mass spectrometry, methods for the study of protein conformations, and protein complexes as well as advanced technologies that may become of practical utility in the coming years. Finally, early examples of the integration of both FTICR approaches to biomedical proteomics applications are presented, along with an outlook for future directions. © 2004 Wiley Periodicals, Inc., Mass Spec Rev 24:168–200, 2005