<p>beta1-adrenergic receptor (β₁-AR) belongs to G protein-coupled receptors, regulating cardiac physiological and pathological process through complex signaling pathways. Physiologically, the activation of β₁-AR produces positive chronotropic, positive inotropic and positive dromotropic effects in the heart. However, excessive or sustained activation of β₁-AR can cause myocardial injury, arrhythmias, and heart failure. The β₁-AR in the heart exhibits tissue-specific distribution patterns and subcellular localization features adapted to its function within cardiomyocytes. Upon ligand binding, the β₁-AR undergoes conformational changes and transmits signaling through G protein-dependent pathways (β₁-AR/Gs and β₁-AR/Gi) as well as a G protein-independent pathway (β₁-AR/β-arrestin) to regulate cardiac activity. Subsequently, the β₁-AR can either dissociate from G protein to undergo desensitization and terminate signal transduction, or it can be endocytosed into the cell, transported to the lysosome to be degraded, or returned to the plasma membrane to continue its function. Additionally, it has been found that β₁-AR can cause or exacerbate heart disease when abnormal changes occur in its distribution density, localization, and mediated downstream signaling pathways. Therefore, β₁-AR represents an important pharmacotherapeutic target for the treatment of cardiac diseases. Among the relevant therapeutic agents, β₁-AR blockers designed specifically against β₁-AR have evolved to the third generation. This review comprehensively analyzes β₁-AR from perspectives including its research history, expression, and distribution in the heart, protein structure, signaling pathways, and associations with cardiac diseases.</p>