Cardiovascular (CV) clinical trials are essential to understand the treatment effects and to follow up the natural progression of CV disease. Biomarkers play a pivotal role in understanding the disease state, risk levels, and clinical decision-making. We review the roles that biomarkers have played in CV clinical trials and roles that CV clinical trials have played and will continue to play in the discovery and validation of biomarkers and their implementation in clinical practice. Biomarkers were once the workhorses of patient selection and endpoint definition in clinical trials; more recently, clinical trials have been the proving ground for individual biomarkers. These markers could also reflect the entire spectrum of disease from the earliest manifestations to the terminal stages. In this paper we review recent advances with the use of biomarkers and a glimpse to the history and future of cardiac markers