Cardiovascular cell-based regenerative medicine has enjoyed a brief but exciting history. In little over a decade, multiple hypotheses have risen and fallen, and this work has now triggered a critical reconsideration of several long-held cardiovascular paradigms. These and other issues were the focus of the second Symposium on Cardiovascular Regenerative Medicine, recently held at the NIH-NHLBI in Bethesda, MD, USA. The meeting served to showcase some of the highlights of the past decade but, at the same time, sharply underlined the enormity of the task ahead. Collectively, a sense emerged that researchers in this field are "digging in for the long haul.".