In recent years, we have seen a great interest in the search for new biomarkers in heart failure (HF), fundamentally in the field of diagnosis, prognosis, monitoring and as a therapeutic guide. However, most of them do not meet the required criteria for daily clinical practice. The carbohydrate antigen 125 (CA 125) is the mucin 16 glycoprotein (MUC16) antibody, and its use has been restricted to the therapeutic monitoring of ovarian cancer; however, its elevation is confirmed in other non-tumour processes such as HF. In this last scenario, CA 125 is synthesised by serous epithelial cells in response to congestion and/or inflammatory stimuli. In recent years, increasing evidence has emerged suggesting that plasma levels of this glycoprotein could be useful as a biomarker in HF. CA 125 levels correlate with clinical, haemodynamic and echocardiographic parameters related to the severity of the disease, as well as being independently associated with mortality or readmission due to HF. From the clinical perspective, CA 125 provides information on the degree of extravascular congestion present in HF. Recent evidence consistently shows that its kinetics after admission due to decompensation offer an excellent predictive capacity for adverse events and to guide treatment, mainly diuretic. These qualities make it an ideal candidate for use in evolutionary monitoring and to guide depletive treatment in HF.