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The interaction between the immune and cardiovascular systems is a growing field of investigation with bidirectional aspects. B cells are modulators of the adaptive and the innate immunity and they orchestrate bone marrow and spleen immune responses beyond infectious diseases. B cell regulation contributes to the pathophysiology of myocardial damage in several conditions including myocardial infarction, heart failure and atherosclerosis. In parallel, B cell-derived hematological disorders are interlinked to cardiovascular complications, including thrombosis and immunoglobulin-related cardiotoxicity. The scope of this review is to summarize the function and role of B cells as important players in myocardial and vascular adaptations to injury and as mediators of cardiovascular adverse events in hematological disorders. The primary focus is to highlight the clinical and preclinical findings regarding B cell-targeted therapies and their positive or negative impact on the cardiovascular system. A deeper understanding of B cell subpopulations, functions, and secretome could lead to targeted therapeutic interventions for cardiovascular and hematologic diseases.