The consequences of pandemic influenza for vulnerable populations will depend partly on the effectiveness of health risk communications. Strategic planning should fully consider how life circumstances, cultural values, and perspectives on risk influence behavior during a pandemic. We summarize recent scientific evidence on communication challenges and examine how sociocultural, economic, psychological, and health factors can jeopardize or facilitate public health interventions that require a cooperative public. If ignored, current communication gaps for vulnerable populations could result in unequal protection across society during an influenza pandemic. We offer insights on communication preparedness gleaned from scientific studies and the deliberations of public health experts at a meeting convened by the Centers for Disease Control and Prevention, May 1 and 2, 2008.