Heart failure (HF) may be considered as the fatal finishing line of all cardiovascular disorders. There is not a single diagnostic test for HF, and its diagnosis relies on clinical judgment based on a combination of history, physical examination, and appropriate investigations. For these reasons, the accuracy of diagnosis by clinical means alone is often inadequate. Despite the enormous advances in understanding and treatment that have taken place during the last 50 years, HF continues to have a poor prognosis. Diagnosis and risk stratification of patients with HF depend on the availability of specific, accurate, and effective disease or risk markers. Thus, there is an increasing interest in the development of new cardiovascular biomarkers, and, consequently, a great number of laboratory tests have recently been proposed for their assay. In this review, we briefly discuss the characteristics of an ideal HF biomarker and describe the analytical performance and clinical relevance of available biomarker assay methods, comparing their performances with that of an ideal biomarker for HF. Finally, we present a scheme to search for more efficient diagnostic and prognostic biomarkers for HF.