Recent interest in mechanisms of stem cell-mediated repair in the heart have spawned the ``paracrine hypothesis'', which posits that stem cells release beneficial substances that improve regeneration and function of the injured and diseased myocardium. In support of this hypothesis are findings that small membranous vesicles called exosomes are released from stem cells and deliver beneficial cargo to cells in the heart. However, in addition to exosomes, which are released by the unconventional secretory pathway, are many other factors released by the unconventional and the conventional secretory pathways. A broader perspective of mechanisms of secretion, as well as an appreciation for the ways in which the secretion of a wide range of different types of molecules can be regulated, will spawn new avenues of thought necessary to move us beyond the exosome-centric view that drives much of the current thinking of the paracrine hypothesis of stem cell-mediated repair in the heart.