Clinical studies have shown that circulating levels of interleukin (IL)-6 and other IL-6 related cytokines are increased in patients with congestive heart failure (CHF). Plasma IL-6 concentrations are related to decreasing functional status of the patient and provide important prognostic information. Experimental studies have produced compelling evidence that IL-6 and IL-6 related cytokines play a pivotal role in the regulation of cardiac myocyte hypertrophy and apoptosis. This review summarizes clinical and experimental data from this rapidly evolving field, which, taken together, strongly suggest that IL-6 and IL-6 related cytokines are intricately involved in the pathophysiology of the failing heart.