In recent years, stem cell therapy for the treatment of heart disease has translated from the imagination of investigators to the bedside of patients. The initial results from trials evaluating cell therapy for the heart are encouraging. As this new field of cellular transplantation matures, it is imperative that novel methodologies for evaluating cell therapy are developed and applied to guide therapy. Molecular imaging is a discipline that is evolving to address these needs and is expected to play an increasing role in the characterization and assessment of cell therapy. This article provides a focused overview of clinical stem cell therapy for the heart, followed by a discussion of how novel molecular imaging techniques are presently being applied to monitor cell therapy.