Recent reviews of the literature have indicated that a number of health communication campaigns continue to fail to adhere to principles of effective campaign design. The lack of an integrated, organizing framework for the design, implementation, and evaluation of health communication campaigns may contribute to this state of affairs. The current article introduces an audience–channel–message–evaluation (ACME) framework that organizes the major principles of health campaign design, implementation, and evaluation. ACME also explicates the relationships and linkages between the varying principles. Insights from ACME include the following: The choice of audience segment(s) to focus on in a campaign affects all other campaign design choices, including message strategy and channel/component options. Although channel selection influences options for message design, choice of message design also influences channel options. Evaluation should not be thought of as a separate activity, but rather should be infused and integrated throughout the campaign design and implementation process, including formative, process, and outcome evaluation activities. Overall, health communication campaigns that adhere to this integrated set of principles of effective campaign design will have a greater chance of success than those using principles idiosyncratically. These design, implementation, and evaluation principles are embodied in the ACME framework.