Sympathetic nerve activities have pivotal roles in pathophysiology and prognosis in patients with heart failure. Among the various available techniques for the analysis of sympathetic nerve function, cardiac neuroimaging with a norepinephrine analogue is a noninvasive, specific and powerful modality that enables in vivo assessment of cardiac sympathetic innervation and activity and has demonstrated pathophysiological alterations at pre-synaptic nerve terminals and their clinical implications. Impaired cardiac metaiodobenzylguanidine (MIBG) activity and, conversely, increased systemic sympathetic function drive closely correlate with clinical outcomes. Cardiac MIBG activities have independent but incremental prognostic values in combination with known clinical determinants in patients with heart failure. Systemic inhibition of sympathetic drive and the rennin-angiotension-aldosterone system can improve cardiac MIBG activity and kinetics together with functional improvement in heart failure patients. Prognostic efficacy of contemporary drug treatment is, however, likely to depend on the severity of the impairment of cardiac MIBG activity. Patients who have impaired cardiac MIBG activity with blunted heart rate variability, an elevated brain natriuretic peptide level or LV dysfunction are likely to have appropriate discharges of an implantable cardioverter defibrillator. Thus, cardiac neuroimaging could enable appropriate selection of patients at greater risk for lethal outcomes, who can probably benefit most from pharmacological and invasive strategies.