Chronic heart failure (CHF) represents a major public health burden, and its prognosis is comparable to that of different malignant diseases. Our understanding of CHF has developed from the rather simplistic model of mere pump failure to that of a multisystem disorder which affects not only the cardiovascular system but also the musculoskeletal, renal, neuroendocrine, and immune systems. Thus, the pathophysiology of CHF is exceedingly complex. Therapies to block excessive neuroendocrine activation have become a cornerstone of treatment. CHF progresses because of activation of neurohormones and pro-inflammatory cytokines following an initial cardiac injury or a mutation of the genetic programme. 1 Virtually any heart disease can ultimately lead to heart failure, although the initial event leading to the development of this syndrome is in many cases unknown. However, CHF is always the result of some underlying process and the diagnosis cannot stand alone. The activation of the aforementioned systems maintains and worsens CHF. In particular, the activation of the immune system has received considerable interest in the last decade. There are several different components to this system which interact with each other in a complex manner. It is becoming increasingly apparent that inflammatory mediators play a crucial role in the development of CHF, and several strategies to counterbalance different aspects of the inflammatory response are considered. Possible targets involve pro-and anti-inflammatory cytokines and their receptors, endotoxin, adhesion molecules, nitric oxide and nitric oxide synthase, reactive oxygen species, and different types of leucocytes. The purpose of this review is to give a brief overview of the current understanding of the role of inflammation in CHF. Furthermore, we will discuss recent advances in the development of new therapeutic strategies in this field.