Cardiovascular proteomics is the branch of proteomics specifically applied to heart and vasculature. The field of proteomics has recently gained greater importance based on its potential to unravel the complex physiological and biochemical mechanisms and pathways in organisms and cells at the molecular level. The goal is to identify proteins that generate/mediate disease process, thereby, opening avenues to new diagnostics and therapeutic strategies. Proteins are much closer to the actual disease process, in most cases, than parent genes. They are the ultimate regulators of cell functions, and the vast majorities serve as drug targets. Differential protein expression analysis, by measuring the upregulated or downregulated proteins in disease state as compared with the normal healthy condition, is vital to understand the disease mechanism. In conjunction with various separation techniques, mass spectrometry (MS)-based methods evolved as the best techniques for the comprehensive characterization of proteins.1,2 After the initial protein identification, a more challenging approach in proteomics is the quantification of the proteins identified.3 Various methods of quantification by MS have been developed recently, for both relative and absolute measurements (Figure 1), and the technology is still expanding to find better and more efficient quantification approaches. This, in turn, is facilitated by the advancements in the MS instrumentation, including powerful analyzers and fragmentation technology. Most of the quantification methods are based on measurements at peptide level and fall under the bottom-up proteomics approach. In this review article, we will outline various MS-based approaches available for measuring the variation in protein abundances and how these techniques are playing a key role in cardiovascular research. Figure 1. An overview of mass spectrometry-based quantitative proteomics: Mass spectrometry (MS)-based quantification can be achieved either by relative or absolute quantification (AQUA). Both relative and AQUA can be further classified into labeled and label-free quantification, each of …