In an age where practicing physicians have access to an overwhelming volume of clinical information and are faced with increasingly complex medical decisions, the ability to execute sound clinical reasoning is essential to optimal patient care. The authors propose two concepts that are philosophically paramount to the future assessment of clinical reasoning in medicine: assessment in the context of “uncertainty” (when, despite all of the information that is available, there is still significant doubt as to the best diagnosis, investigation, or treatment), and acknowledging that it is entirely possible (and reasonable) to have more than “one correct answer.” The purpose of this article is to highlight key elements related to these two core concepts and discuss genuine barriers that currently exist on the pathway to creating such assessments. These include acknowledging situations of uncertainty, creating clear frameworks that define progressive levels of clinical reasoning skills, providing validity evidence to increase the defensibility of such assessments, considering the comparative feasibility with other forms of assessment, and developing strategies to evaluate the impact of these assessment methods on future learning and practice. The authors recommend that concerted efforts be directed toward these key areas to help advance the field of clinical reasoning assessment, improve the clinical care decisions made by current and future physicians, and have positive outcomes for patients. It is anticipated that these and subsequent efforts will aid in reaching the goal of making future assessment in medical education more representative of current-day clinical reasoning and decision making.