Leukocyte behavior plays a critical role in the progression and complications of cardiovascular diseases, including atherosclerosis, myocardial infarction (MI), and heart failure. Atherosclerosis is a chronic inflammatory disease driven by lipids and leukocytes, leading to life-threatening events such as MI and stroke. Survivors of MI may develop heart failure, a chronic condition of inadequate heart function. Leukocytes, including macrophages, monocytes, neutrophils, mast cells, and platelets, are involved in both protective and harmful processes during these diseases. In atherosclerosis, macrophages ingest lipids, forming foam cells that contribute to lesion development. However, foam cell formation can suppress inflammatory gene expression. Monocytes, particularly Ly-6C high monocytes, migrate to atherosclerotic lesions, where they differentiate into macrophages. Ly-6C low monocytes, on the other hand, are involved in tissue repair. Leukocyte subsets can be either atherogenic or atheroprotective, and their balance is crucial for disease progression. In MI, leukocytes such as neutrophils and monocytes are recruited to the infarct site, where they contribute to inflammation and tissue repair. Neutrophils phagocytose dead tissue and release inflammatory mediators, while Ly-6C high and Ly-6C low monocytes play distinct roles in the healing process. Monocytes can also migrate to non-ischemic regions, contributing to heart failure through mechanisms such as ventricular dilation and fibrosis. Adaptive immunity, involving T cells and B cells, also plays a role in atherosclerosis. T helper cells, particularly Th1 and Th17, promote inflammation, while Th2 and regulatory T cells are protective. B cells can be both atheroprotective and atherogenic, depending on their subset. Leukocytes are integral to the systemic response to MI, contributing to atherosclerosis progression and heart failure. Leukocyte activity post-MI is a therapeutic target for secondary prevention. Understanding the complex interactions between leukocytes and other cells in the cardiovascular system is essential for developing targeted therapies. Animal models and human studies highlight the importance of leukocyte subsets in disease progression and the potential for therapeutic interventions targeting specific leukocyte functions.Leukocyte behavior plays a critical role in the progression and complications of cardiovascular diseases, including atherosclerosis, myocardial infarction (MI), and heart failure. Atherosclerosis is a chronic inflammatory disease driven by lipids and leukocytes, leading to life-threatening events such as MI and stroke. Survivors of MI may develop heart failure, a chronic condition of inadequate heart function. Leukocytes, including macrophages, monocytes, neutrophils, mast cells, and platelets, are involved in both protective and harmful processes during these diseases. In atherosclerosis, macrophages ingest lipids, forming foam cells that contribute to lesion development. However, foam cell formation can suppress inflammatory gene expression. Monocytes, particularly Ly-6C high monocytes, migrate to atherosclerotic lesions, where they differentiate into macrophages. Ly-6C low monocytes, on the other hand, are involved in tissue repair. Leukocyte subsets can be either atherogenic or atheroprotective, and their balance is crucial for disease progression. In MI, leukocytes such as neutrophils and monocytes are recruited to the infarct site, where they contribute to inflammation and tissue repair. Neutrophils phagocytose dead tissue and release inflammatory mediators, while Ly-6C high and Ly-6C low monocytes play distinct roles in the healing process. Monocytes can also migrate to non-ischemic regions, contributing to heart failure through mechanisms such as ventricular dilation and fibrosis. Adaptive immunity, involving T cells and B cells, also plays a role in atherosclerosis. T helper cells, particularly Th1 and Th17, promote inflammation, while Th2 and regulatory T cells are protective. B cells can be both atheroprotective and atherogenic, depending on their subset. Leukocytes are integral to the systemic response to MI, contributing to atherosclerosis progression and heart failure. Leukocyte activity post-MI is a therapeutic target for secondary prevention. Understanding the complex interactions between leukocytes and other cells in the cardiovascular system is essential for developing targeted therapies. Animal models and human studies highlight the importance of leukocyte subsets in disease progression and the potential for therapeutic interventions targeting specific leukocyte functions.