Despite remarkable advances in basic biomedical science that have led to improved patient care, there is a wide and persistent gap in the abilities of researchers and clinicians to understand and appreciate each other. In this Editorial, the authors, a scientist and a clinician, discuss the rift between practitioners of laboratory research and clinical medicine. Using their first-hand experience and numerous interviews throughout the United States, they explore the causes of this 'cultural divide'. Members of both professions use advanced problem-solving skills and typically embark on their career paths with a deeply felt sense of purpose. Nonetheless, differences in classroom education, professional training environments, reward mechanisms and sources of drive contribute to obstacles that inhibit communication, mutual respect and productive collaboration. More than a sociological curiosity, the cultural divide is a significant barrier to the bench-to-bedside goals of translational medicine. Understanding its roots is the first step towards bridging the gap.