The prevalence of congestive heart failure is progressively increasing and despite recent advances in therapeutics, there is a continuing need for novel effective therapies. New, investigational treatment strategies include inotropic drugs, neurohormonal antagonists, anticytokine and anti-inflammatory strategies, hormonal therapies, and nutritional supplements. Current positive inotropes (eg, dobutamine and phosphodiesterase inhibitors) provide symptomatic relief, but newer agents may have a better adverse effect profile. Angiotensin-converting enzyme (ACE) inhibitors should remain first-line treatment with angiotensin receptor blockers used in ACE inhibitor-intolerant patients. Many new neurohormonal antagonists have recently been investigated and eplerenone has demonstrated clinical benefit. New hormonal, anticytokine, and anti-inflammatory therapies have shown benefit in small trials, but results in larger trials have been disappointing. Other approaches are currently being tested in large trials that will clarify their role. Nutritional supplements need to be tested in a large prospective trial before they can be recommended.