Due to their remarkable plasticity, macrophages can adapt to diverse environments and challenges therein, thereby exerting tissue-specific and context-specific functions. Macrophages are the most frequent immune cell population present in the heart and contribute substantially to cardiac homeostasis and function. Moreover, macrophages are key regulators throughout all stages of heart injury, acquiring diverse phenotypes that can either ameliorate or exacerbate cardiac pathology in a context-dependent manner. The contribution of macrophages to both tissue damage as well as to recovery/tissue repair during heart injury provides avenues for therapeutic modulation of their functions to beneficially influence heart injury progression and hence prevent heart failure. However, to effectively fine-tune macrophage function, a deep understanding of their heterogeneity is required. The present review focuses on the phenotypic diversity and different roles of macrophages in cardiac homeostasis as well as in ischemic and non-ischemic heart disease, and discusses macrophages as potential therapeutic targets in the settings of heart injury.