Gene- and cell-based therapeutic procedures have entered the cardiovascular field. Many of these novel interventions aim at cardiac regeneration and the initial experimental groundwork has been promising. But early clinical experience did not always confirm the experimental findings and it is felt that the full potential of cardiac gene and cell therapy has, by far, not been exploited. Conflicting clinical results emphasise the need for powerful non-invasive tools to monitor the success of therapy and identify most suitable candidates. As reviewed here, established clinical cardiac imaging tools, together with novel molecular-targeted approaches, are expected to advance the field of myocardial regeneration and to expedite progress and clinical translation.