Several targets for heart failure therapy may be met through different mechanisms which are not necessarily associated. In the Australia/New Zealand Heart Failure Research Collaborative Group Study, patients with chronic stable heart failure of ischaemic aetiology on treatment including ACE inhibitors were randomized to treatment with either the vasodilator beta-blocking drug carvedilol or placebo. At 12 months, symptoms and exercise performance were unchanged, but ejection fraction increased significantly with carvedilol treatment; at 20 months, the rate of death and hospitalization was also significantly reduced in the carvedilol-treated group. In a sub-study using two dimensional echocardiography, progressive left ventricular (LV) dilatation occurred in the placebo group, compared with significant reductions in LV volumes with the carvedilol treatment group. An overview of all available carvedilol trial data showed the odds of death reduced by one-half with treatment (OR 0.51, 95% CI 0.33-0.77, 2P = 0.0014). Thus, improved LV remodelling occurs with carvedilol treatment in heart failure and is associated with improved long-term outcomes including survival. Improved LV function may, in part, mediate the survival benefit of carvedilol and provide a reliable surrogate for long-term outcomes.