Physician scientists (researchers with either MD or MD-Ph. D. degrees) have the unique potential to combine clinical perspectives with scientific insight, and their participation in biomedical research has long been an important topic for policymakers and educators. Given the recent changes in the research environment, an update and extension of earlier studies of this population was needed. Our findings show that physician scientists are less likely to take a major role in biomedical research than they were in the past. The number of physician scientists receiving postdoctoral research training and career development awards is at an all-time low. Physician scientists today, on average, receive their first major research award (R01 equivalent) at a later age than in the 1980s. The number of first-time R01-equivalent awards to physicians is at the same level as it was 30 yr ago, but physicians now represent a smaller percentage of the grant recipients. The long-term decline in the number of physicians entering research careers was temporarily halted during the period of substantial US National Institutes of Health (NIH) budget growth (1998–2003). These gains are lost, however, in the subsequent years when NIH budgets failed to keep pace with rising costs.—Garrison, HH, Deschamps, AM NIH research funding and early career physician scientists: continuing challenges in the 21st century.