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Heart failure (HF) is a heterogeneous condition with a prevalence of about 1-3% in the population worldwide (percentage expected to rise), related to a significant clinical and economic burden. However, despite medical advancements in HF management, difficulties in facing this condition still persist, as the etiology and phenotype largely differ between patients. Thus, the identification of further key biomarkers remains attractive. One area of interest in recent years has focused on the role of lipids in HF pathophysiology and its clinical manifestations. In this context, ceramides, complex bioactive lipids with activity in key pathways related to stress response, cellular growth, proliferation, differentiation, apoptosis, oxidative stress, inflammation, and energy production, may be important in the HF scenario, primarily for the development and application of new therapeutic strategies targeting ceramide species. Accordingly, this review aims to discuss the role of ceramides in HF pathophysiology and clinical progression in view of available evidence, focusing on the possibility of therapeutic tools for improving cardiac function and outcomes in HF by modulating ceramide signaling and metabolism.