Myocardial damage, by different noxious causes, triggers an inflammatory reaction driving post-injury repair mechanisms and chronic remodelling processes that are largely detrimental to cardiac function. Cardiomyocytes have recently emerged as key players in orchestrating this inflammatory response. Injured cardiomyocytes release damage-associated molecular pattern molecules, such as high-mobility group box 1 (HMGB1), DNA fragments, heat shock proteins, and matricellular proteins, which instruct surrounding healthy cadiomyocytes to produce inflammatory mediators. These mediators, mainly interleukin (IL)-1β, IL-6, macrophage chemoattractant protein (MCP)-1, and tumour necrosis factor α (TNF-α), in turn activate versatile signalling networks within surviving cardiomyocytes and trigger leucocyte activation and recruitment. In this review, we will focus on recently characterized signalling pathways activated in cardiomyocytes that mediate inflammatory responses during myocardial infarction, hypertensive heart disease, and myocarditis.