Vaccine hesitancy is one of the greatest health care challenges of our time, as recently highlighted by the experience with COVID-19 vaccines. It is now clear that several current COVID-19 vaccines are highly effective in preventing severe disease, hospitalization, and death from the disease, but their effectiveness has been greatly undermined by the many unfounded conspiracy theories, active disinformation, and fears (real or imagined) circulating through social media and through society in general, persuading millions of people worldwide not to receive the vaccine. Fortunately, there are numerous practical strategies that physicians and other health care professionals can employ in communicating effectively with vaccine-hesitant individuals, including using humble inquiry, compassionate listening, and storytelling, as well as engaging the entire health care team in providing accurate information. This article summarizes the major points of an IAS-USA-sponsored webinar held on August 3, 2021, titled COVID-19 Vaccine Hesitancy, Crucial Conversations, and Effective Messaging for Patients and Health Care Teams by Marie T. Brown, MD, an expert on adult immunization. The webinar was moderated by Constance A. Benson, MD.