Physician-scientists, in the eyes of the National Institutes of Health (NIH), are crucial to the biomedical research enterprise since the development of evidence-based practice based on cutting-edge research. At the same time, NIH has heightened the importance of research mentorship by permitting investigators to revise an application a single time. The current NIH approach, therefore, narrows the margin of error allowable in a proposal and requires that investigators fully develop research protocols for initial submission. The purpose of this manuscript, therefore, is to provide medical toxicologists with a proven research methodology that can be applied to substance abuse investigations. A secondary aim is to provide successful grant language that can be used in subsequent applications for research funding.