Therapeutic trials represent the front line of clinical progress, where the rubber meets the road. The conduct of clinical trials requires unique skills, innate as well as learned, on the part of the investigators who conduct these studies. Often such skills are acquired onthe jobandare passedonfrommentor to junior investigator.However,over the years, the role of the principal investigator (PI) has evolved into a vast list of roles and responsibilities that cannot readily be conveyed through a hands-on approach alone. The fast-paced tempo of drug discovery and development, and the ever-increasing numbers of therapeutic trials being conducted in theUnited States, combinedwith a decline in the number of new clinical investigators, haveexposeda gapbetweenthe expectationsplacedonthe PIandthetraining and experience of today's young clinicians, who are being asked to take on the responsibilities outlined in Food andDrugAdministration Form1572. This article aims to begin an exploration of the role and increasing responsibilities of a PI and the growing need for structured investigator training.We propose options to better equip the PI to achieve compliance with Good Clinical Practice.