Professor Attilio Maseri is a clinical investigator with a remarkable track record of innovative research who, by changing traditional paradigms, contributed to shape new diagnostic techniques in pathophysiologic thinking. His research has been characterized by challenging the generalizations of accepted "wisdom" which did not offer satisfactory explanations for the observations he made in his clinical practice. The results of his clinical investigations have contributed greatly to the opening of new avenues of research and patient management in the field of ischemic heart disease. His clinical and research experiences are catalogued in 740 pages of his single-authored textbook Ischemic Heart Disease. A Rational Basis for Clinical Practice and Clinical Research. This book chronicles Maseri's novel unifying vision of ischemic heart disease. In 2001, Professor Maseri left Catholic University in Rome to take on bigger challenges in Milan where he is now functioning as Professor of Cardiology at the University Vita-Salute San Raffaele and Director of the Cardio-Thoracic and Vascular Department of the San Raffaele Scientific Institute. His research interests include application of molecular biology, differential gene expression profiling, and clinical cardiovascular research such as molecular mechanisms of coronary instability and molecular mechanisms of negative and positive ventricular remodeling. Professor Attilio Maseri will be remembered as a thoughtful clinician, a mentor for many whose academic careers have blossomed, and a careful clinical investigator whose innovative research in ischemic heart disease will set the highest standards for those who follow in his giant footsteps. On a personal note, I first met Attilio Maseri, his wife Francesca, and their son Filippo at the 1976 Pisa conference. What transpired at that conference influenced my own career and stimulated my continued interest in ischemic heart disease as well as my enthusiasm for the international aspects of cardiovascular medicine. I consider myself fortunate to be a friend of Attilio Maseri and to have benefited from my associations with him, both professionally and personally.