Early diagnosis of cardiovascular disease (CVD) is critically important for successful treatment and recovery of patients. At present, detection of CVD at early stages of its progression becomes a major issue for world health. The nanoscale electrochemical biosensors exhibit diverse outstanding properties, rendering them extremely suitable for the determination of CVD biomarkers at very low concentrations in biological fluids. The unique advantages offered by electrochemical biosensors in terms of sensitivity and stability imparted by nanostructuring the electrode surface together with high affinity and selectivity of bioreceptors have led to the development of new electrochemical biosensing strategies that have introduced as interesting alternatives to conventional methodologies for clinical diagnostics of CVD. This review provides an updated overview of selected examples during the period 2005–2018 involving electrochemical biosensing approaches and signal amplification strategies based on nanomaterials, which have been applied for determination of CVD biomarkers. The studied CVD biomarkers include AXL receptor tyrosine kinase, apolipoproteins, cholesterol, C-reactive protein (CRP), D-dimer, fibrinogen (Fib), glucose, insulin, interleukins, lipoproteins, myoglobin, N-terminal pro-B-type natriuretic peptide (BNP), tumor necrosis factor alpha (TNF-α) and troponins (Tns) on electrochemical transduction format. Identification of new specific CVD biomarkers, multiplex bioassay for the simultaneous determination of biomarkers, emergence of microfluidic biosensors, real-time analysis of biomarkers and point of care validation with high sensitivity and selectivity are the major challenges for future research.