Proteomic technologies are used to study the complexity of proteins, their roles, and biological functions. It is based on the premise that the diversity of proteins, comprising their isoforms, and posttranslational modifications (PTMs) underlies biology. Based on an annotated human cardiac protein database, 62% have at least one PTM (phosphorylation currently dominating), whereas ≈25% have more than one type of modification. The field of proteomics strives to observe and quantify this protein diversity. It represents a broad group of technologies and methods arising from analytic protein biochemistry, analytic separation, mass spectrometry, and bioinformatics. Since the 1990s, the application of proteomic analysis has been increasingly used in cardiovascular research. Technology development and adaptation have been at the heart of this progress. Technology undergoes a maturation, becoming routine and ultimately obsolete, being replaced by newer methods. Because of extensive methodological improvements, many proteomic studies today observe 1000 to 5000 proteins. Only 5 years ago, this was not feasible. Even so, there are still road blocks. Nowadays, there is a focus on obtaining better characterization of protein isoforms and specific PTMs. Consequently, new techniques for identification and quantification of modified amino acid residues are required, as is the assessment of single-nucleotide polymorphisms in addition to determination of the structural and functional consequences. In this series, 4 articles provide concrete examples of how proteomics can be incorporated into cardiovascular research and address specific biological questions. They also illustrate how novel discoveries can be made and how proteomic technology has continued to evolve.