In patients with impaired myocardial contractility associated with downregulation of the beta-receptors, compounds inhibiting phosphodiesterase (PDE) 3 may be useful to increase contractility. The PDE3 inhibitor enoximone has been shown to improve pump-function independent from the beta-receptor pathway. A simultaneous decrease in ventricular preload and afterload by vasodilation has led to the term 'inodilator'. Esmolol is the only available ultra-short acting intravenous beta-blocking agent. Due to its half-life of approximately 9 min, beta-blockade, and thus, heart rate, can easily be titrated. Esmolol appears to be a helpful tool to avoid myocardial ischemia (e.g., in the perioperative setting). As with all other beta-blockers, it has dose-dependent negative inotropic effects, and this limits its use in patients with severe heart failure showing low cardiac output. It seems reasonable that an intravenous combination of both approaches, enoximone-induced positive inotropy and esmolol-associated protection from myocardial ischemia, might offer advantages by producing beneficial hemodynamic effects and by compensating each other's limitations in a complementary way. In spite of some promising results, the place of a combination of enoximone and esmolol in the process of treating patients with (acute) heart failure showing low output is still not entirely clear, and needs further confirmation.