Heart failure (HF) is a complex syndrome with cardiac, renal, neurohormonal and sympathetic nervous system's manifestations, the pathogenesis of which among others is connected to inflammation. PAF has local and systemic effects pertaining to HF progression since it causes a negative inotropic effect, it induces arrhythmias, it induces apoptosis and it is involved in inflammation and atherosclerosis. In the present review the role of PAF in HF will be thoroughly presented along with the relevant data on PAF enzymes and the potential role of PAF metabolic circuit as a novel pharmacological target.