Cardiovascular proteomics has grown rapidly in the intervening period, with >400 studies now being published yearly (Fig. 1) [3]. To put into context, we recall two landmark reviews of cardiovascular proteomics, in 2001 [4] and 2006 [5], which noted that although many enabling technologies were emerging, cardiovascular proteomics remained a field ‘on the threshold’ of future applications. Fast forward to the present and it is clear that proteomics has had a transformative impact on cardiovascular sciences, as recounted in recent review articles. We attempt to complement these reviews here with a concise overview on the lockstep improvements in the analytical (separation sciences and mass spectrometry) and computational (data science and algorithms) advances of the past 5 years that enabled landmark studies, as well as ongoing developments driving the next stage of applications. Fig. 1 Trends in cardiovascular proteomics. Both (a) the volume of proteomics studies, and (b) the size of proteomics dataset have skyrocketed in the last decade. a The number of cardiovascular proteomics studies has increased approximately 400 % from 2004 to 2014, far outpacing the natural growth of the cardiovascular field, indicating increasingly common adoption of the technologies. b The protein coverage of proteomics experiments in the same time period has experienced considerable growth also, quantified as the numbers of identifiable cardiac proteins in an experiment. The maximum number of cardiac proteins (dashed lines) is based on estimated significantly expressed loci in the mouse heart and does not take into account proteoforms such as resulting from alternative splicing. This increase is driven by parallel advances in hardware instrumentation and computational technology. Coinciding with the notion of “complete proteomics”, proteomics studies can now interrogate more proteins of interest such as chromatin remodeling factors and transcription factors that express at low copy numbers. Effective means to analyze big proteomics dataset are becoming a new frontier of growth in cardiovascular proteomics