Acute myocardial infarction (MI) provokes a systemic inflammatory response that may contribute to the development of left ventricular systolic dysfunction (LVSD) and heart failure (HF). Patients with post-infarct HF with concomitant LVSD have the most unfavourable long-term prognosis. Measurement of C-reactive protein (CRP) concentration reflecting an involvement of inflammatory pathways in post-infarct myocardial damage offers an attractive strategy to improve risk stratification and clinical decision-making for early management of high-risk patients. Despite growing evidence for the prognostic value of CRP both as a single factor and as a component of multi-marker approach in MI, CRP measurement is not yet incorporated into current guidelines. This may be due to conflicting results reported in existing studies related to various limitations in study designs, such as retrospective case control design, prior myocardial damage, CRP measurement with low-sensitivity assays, non-homogenous populations with acute coronary syndromes, different treatment strategies, small sample sizes, and the lack of left ventricular ejection fraction assessment and long-term clinical and echocardiographic monitoring. As a result, previous studies have not provided conclusive evidence of the prognostic value of CRP for post-infarct LVSD or HF. Future studies with an adequate design including upstream mediators of inflammation as inflammatory markers are needed to identify the best biomarker-based strategies for identifying high-risk patients. Further clinical trials involving anti-inflammatory therapies target-ing different pathways of inflammatory activation in MI should test the inflammatory hypothesis of post-infarct LVSD and HF. Identifying high-risk patients with persistent post-infarct inflammatory response may allow incorporation of pathophysiological guidance for implementation of personalised treatment approaches.