According to the World Health Organization (WHO), cardiovascular diseases are the leading cause of death worldwide. Several diseases have been linked to changes in cellular mechanical properties, including those affecting the heart. Atomic force microscopy (AFM) has proven to be one of the most effective techniques for precisely determining the topography and mechanical properties of adherent living cells. In this review, we provide a short chronological overview of key studies conducted using AFM on cardiac cells or cardiomyocytes with clinical and medical significance. These studies have contributed and continue to enhance our understanding of the pathological processes affecting the heart and clarify the role of cell mechanics in cardiac and cardiovascular diseases.