In 2012, we lost three pioneers: Robert S. Ledley in Biomedical Imaging, Moses Greenfield in Medical Physics, and Hooshang Kangarloo in PACS and Informatics. They had their own respective background, interest, and contribution to science and technology that cemented certain cornerstones of today’s Biomedical Imaging Informatics. Among other accomplishments, this memory focuses on their contributions related to medical imaging, medical physics, PACS and informatics. The evolution of medical imaging informatics can be traced from the footprints of these three pioneers through the time line shown in the last figure in the paper. Their dedication in contributing to this field would be remembered by their students, fellows and colleagues who are now continuously leading the growth in this field of science and technology.