Health promotion is a complex communication process that involves identifying and recommending adoption of the best available evidence-based guidelines for addressing the most dangerous health risks confronting modern society. Despite the steady proliferation of major scientific advances in knowledge about the best available strategies for preventing and responding to many of these health risks, it has been frustratingly difficult to mobilize widespread adoption of recommended evidence-based health promotion guidelines by at-risk populations around the globe. Even worse, there has been a growing number of frustrating instances of active public resistance to adopting evidence-based public health guidelines concerning participation in screening efforts for detecting dangerous health risks as early as possible (when many health risks are most responsive to treatment), getting vaccinated help build public immunity to deadly infectious diseases, actively seeking needed health care to address health problems, following health care recommendations (including adhering with prescribed medications and treatment regimens), as well as integrating important behavioral practices into daily living, such as good nutrition, regular exercise, and strategies to prevent the spread of disease (like social distancing and wearing protective masks in public settings to reduce the spread of airborne infectious diseases). Effective health communication is needed to help members of the public, especially those who are at greatest risk for poor health outcomes (such as elderly, homeless, disenfranchised, disabled, immigrant, and those suffering from multiple co-morbidities) to recognize the seriousness and salience of public health threats, engage in recommended actions to minimize the likelihood of contracting these health problems, and to respond effectively when they encounter serious health risks. This article examines the significant challenges to communicating relevant health information to those who are confronting serious health risks, especially to members of the most vulnerable populations, and suggests strategies for effectively using communication messages and media for promoting adoption of recommended health promotion actions.