Heart failure is a growing global epidemic that involves in its pathophysiology a proinflammatory state. Since the first description of elevated cytokine levels in this setting, there has been increasing interest in understanding the role of these molecules in left-ventricular remodeling and function. Over the years, intense research on the 'cytokine theory' of heart failure has allowed evaluation of the role of inflammatory biomarkers not only as pathogenetic mediators, but also as potential tools in the diagnosis and risk stratification of heart failure patients. Whereas current evidence does not support the use of inflammatory biomarkers for the diagnosis of heart failure, the assessment of their levels and the connection between their changes and changes in clinical status and prognosis has been well validated. At present, the utility of anti-inflammatory therapies in heart failure is still debated, since trials of anti-inflammatory agents in this setting have pointed out controversial results. On the contrary, established treatments of heart failure, including β-blockers, renin-angiotensin system antagonists, and aldosterone-receptor blockers seem able to act by modulating cytokine expression, suggesting a new role for these molecules in guiding heart failure therapy. Therefore, the binomial topic of heart failure and inflammation still has a number of fields not completely explored: our aim is to update current knowledge and future perspectives.