The development and subsequent clinical application of the β-adrenergic receptor blocking drugs represent one of the major advances in human pharmacotherapeutics. No other class of synthetic drugs has demonstrated such widespread therapeutic utility for the treatment and prevention of so many cardiovascular diseases. In addition, these drugs have proven to be molecular probes that have contributed to our understanding of the disease, and on the molecular level, both the structure and function of the 7 transmembrane G protein receptors that mediate the actions of many different hormones, neurotransmitters, and drugs. The evolution of β-blocker drug development has led to refinements in their pharmacodynamic actions that include agents with relative β1-selectivity, partial agonist activity, concomitant α-adrenergic blockers activity, and direct vasodilator activity. In addition, long-acting and ultra-short-acting formulations of β-blockers have also demonstrated a remarkable record of clinical safety in patients of all ages.