Cheyne-Stokes respiration (CSR) is associated with increased mortality among patients with heart failure. However, the specific link between CSR and mortality remains unclear. One possibility is that CSR results in excitation of the sympathetic nervous system. This review relates evidence that CSR exerts acute effects on the autonomic nervous system during sleep, and thereby influences a number of cardiovascular phenomena, including heart rate, blood pressure, atrioventricular conduction, and ventricular ectopy. In patients in sinus rhythm, heart rate and blood pressure oscillate during CSR in association with respiratory oscillations, such that both peak heart rate and blood pressure occur during the hyperpneic phase. Inhalation of CO2 abolishes both CSR and the associated oscillations in heart rate and blood pressure. In contrast, O2 inhalation sufficient to eliminate hypoxic dips has no significant effect on CSR, heart rate, or blood pressure. In patients with atrial fibrillation, ventricular rate oscillates in association with CSR despite the absence of within-breath respiratory arrhythmia. The comparison of RR intervals between the apneic and hyperpneic phases of CSR indicates that this breathing disorder exerts its effect on ventricular rate by inducing cyclical changes in atrioventricular node conduction properties. In patients with frequent ventricular premature beats (VPBs), VPBs occur more frequently during the hyperpneic phase than the apneic phase of CSR. VPB frequency is also higher during periods of CSR than during periods of regular breathing, with or without correction of hypoxia. In summary, CSR exerts multiple effects on the cardiovascular system that are likely manifestations of respiratory modulation of autonomic activity. It is speculated that the rhythmic oscillations in autonomic tone brought about by CSR may ultimately contribute to the sympatho-excitation and increased mortality long observed in patients with heart failure and CSR.