Even 200 years following the conclusion of the Lewis and Clark Expedition, questions remain about whether Meriwether Lewis' death was a suicide. The purpose of this article is to consider this issue by examining historical evidence from a psychological perspective. A risk factor model for suicide assessment (Sanchez, 2001) is employed to evaluate the nature of Lewis' historical, personal, psychosocial environmental, and clinical risk factors as well as protective factors. The authors conclude that though there is some evidence to support a theory of murder, Lewis was at a high suicide risk at the time of his death, and that the preponderance of the evidence indicates that he died by his own hand.