Research during the last decade has generated numerous insights on the presence, phenotype, and function of myeloid cells in cardiovascular organs. Newer tools with improved detection sensitivities revealed sizable populations of tissue-resident macrophages in all major healthy tissues. The heart and blood vessels contain robust numbers of these cells; for instance, 8% of noncardiomyocytes in the heart are macrophages. This number and the cell’s phenotype change dramatically in disease conditions. While steady-state macrophages are mostly monocyte independent, macrophages residing in the inflamed vascular wall and the diseased heart derive from hematopoietic organs. In this review, we will highlight signals that regulate macrophage supply and function, imaging applications that can detect changes in cell numbers and phenotype, and opportunities to modulate cardiovascular inflammation by targeting macrophage biology. We strive to provide a systems-wide picture, i.e., to focus not only on cardiovascular organs but also on tissues involved in regulating cell supply and phenotype, as well as comorbidities that promote cardiovascular disease. We will summarize current developments at the intersection of immunology, detection technology, and cardiovascular health.