Heart failure (HF) is associated with sympathetic overactivity, which contributes to disease progression and arrhythmia development. Cardiac sympathetic innervation imaging can be performed using radiotracers that are taken up in the presynaptic nerve terminal of sympathetic nerves. The commonly used radiotracers are (123)I-metaiodobenzylguanidine ((123)I-mIBG) for planar and single-photon emission computed tomography imaging, and (11)C-hydroxyephedrine for positron emission tomography imaging. Sympathetic innervation imaging has been used in assessing prognosis, response to treatment, risk of ventricular arrhythmias and sudden death and prediction of response to cardiac resynchronization therapy in patients with HF. Other potential applications of these techniques are in patients with chemotherapy-induced cardiomyopathy, predicting myocardial recovery in patients with left ventricular assist devices, and assessing reinnervation following cardiac transplantation. There is a lack of standardization with respect to technique of (123)I-mIBG imaging that needs to be overcome for the imaging modality to gain popularity in clinical practice.