Managing difficult conversations is an important skill to develop and refine for all professionals and future leaders, particularly for those in health care where difficult situations with high stakes are prevalent. The intensity and frequency of these types of conversations will predictably increase as one’s professional responsibility grows. In this article, the authors discuss their interprofessional course, Managing Difficult Conversations, developed 15 years ago for medical and graduate students at Stanford University. The course facilitates the practice of managing difficult conversations through role play in a low-risk, safe classroom setting among peers. The role-played difficult conversations are based upon a series of case studies and are facilitated by faculty and guest experts. There is no single communication style that suits everyone, but the authors offer resources from the course that can be applied for effective difficult conversations, including 12 guiding principles and a 3-stage framework for planning, beginning, and conducting the conversation. Preparing and practicing for difficult conversations will enhance the likelihood of conveying the necessary information with professionalism, directness, clarity, empathy, and warmth. Although unsettling news will always be difficult to receive, the method of delivery should be a source of comfort and hope, not one of discomfort and pain.