G protein-coupled receptors (GPCRs) represent a family of membrane proteins that regulate several cellular processes. Among the GPCRs, G protein-coupled receptor kinases (GRKs) regulate downstream signaling pathways and receptor desensitization. GRK2 has gained significant interest due to its cardiovascular physiology and pathological involvement. GRK2's presence in cardiac tissue and its influence on cardiac function, β-adrenergic signaling, and myocardial remodeling underlies its involvement in cardiovascular diseases such as heart failure and ischemia. GRK2's canonical role is receptor desensitization, but emerging evidence suggests its involvement in mitochondrial dynamics and bioenergetics, influencing processes such as oxidative phosphorylation, reactive oxygen species production, and apoptosis. Moreover, GRK2's localization within mitochondria suggests a direct role in regulating mitochondrial health and function. Notably, while GRK2 inhibition seems to be a therapeutic approach to heart failure, its precise role in mitochondrial dynamics and pathology needs further investigation. This review explores the complex relationship between mitochondrial function and GRK2 and clarifies the implications for cardiovascular health. Cardiovascular medicine might greatly benefit from future studies that focus on understanding the processes behind GRK2-mitochondrial crosstalk to develop personalized therapies.