Chronic heart failure (CHF) is a global medical, social and economic problem. Currently, the search and study of new biomarkers that can provide early diagnosis of CHF, serve as a laboratory tool for assessing the effectiveness of treatment, or be used as prognostic markers and risk stratification criteria are ongoing. Scientists' interest is focused, in particular, on studying the role of fibroblast growth factor 21 (FGF21) in CHF. There is increasing evidence highlighting the value of FGF21 as a new marker for the diagnosis and assessment of prognosis in patients with CHF. The role of FGF21 in CHF is very interesting due to its cardioprotective aspects. Final confirmation of the diagnostic, prognostic and therapeutic roles of FGF21 will come from future studies.