Heart disease remains the leading cause of morbidity and mortality worldwide. With the advancement of modern technology, the role(s) of microtubules in the pathogenesis of heart disease has become increasingly apparent, though currently there are limited treatments targeting microtubule-relevant mechanisms. Here, we review the functions of microtubules in the cardiovascular system and their specific adaptive and pathological phenotypes in cardiac disorders. We further explore the use of microtubule-targeting drugs and highlight promising druggable therapeutic targets for the future treatment of heart diseases.