Much work remains to be done in elucidating the role of specific signaling pathways first in animal models of cardiac disease and then in clinical settings. Animal studies have begun to implicate specific pathways in the pathogenesis of a variety of cardiac conditions including cardiac hypertrophy, contractile dysfunction, and cardiomyocyte loss through programmed cell death. Initial extrapolation of this work to clinical studies will continue to be done on tissue samples obtained at biopsy or explant. However, the ability to assess specific signaling pathways in vivo would greatly facilitate both a more detailed analysis of their clinical contribution to disease and the application of clinical insights gained. Although the subtlety and diversity of signal transduction pathways make this a formidable challenge, development of techniques to noninvasively assess expression of relevant endogenous signaling molecules would be a significant advance over existing technologies. Such a method could yield substantial clinical benefits and enable noninvasive imaging to fully tap into ongoing developments in molecular biology. Moreover, this technology would provide important support for ongoing efforts to develop novel therapeutic approaches, including genetic therapies.