Both scientists and the public are increasingly identifying and reacting to risks associated with wildlife and vector-borne diseases. This trend presents wildlife managers, public health officials, and others (e.g., vector management specialists) with an unprecedented need to communicate effectively about disease risks. Risk communication, described as an exchange of information about the assessment, evaluation, characterization, and management of risk, can help alleviate (a) public misinformation or lack of information about a disease and its associated effects and/or (b) a management entity's lack of understanding of public concerns. For either goal, communication design would benefit from an understanding of how people (individuals or a population aggregately) perceive and react to risks they associate with wildlife disease. Apprehending risk perceptions and reactions is a complicated process. Leading risk perception theorists generally agree that myriad factors influence individuals' beliefs about and responses to risks. The Social Amplification of Risk Framework (SARF), the most comprehensive explanation of risk perceptions and reactions, suggests that cultural, social, and psychological factors work in concert to affect risk perceptions and reactions. The SARF identifies multiple factors, but is not as useful for explaining how perceptions and reactions are affected or identifying the process(es) by which the factors jointly operate. I studied the ways in which individuals perceived and responded to risks associated with wildlife and vector-borne diseases in an effort to increase understanding of how people perceive and react to these risks. Most studies on perceptions of wildlife disease risk have examined the magnitude of risk perceptions as opposed to the reasons for these perceptions. Knowledge of the reasons for risk perceptions and reactions could explicate the modes of communication about a risk that are best suited to certain audiences. I conducted case studies in four geographically- and culturally-diverse communities in and around US national parks to investigate perceptions of and reactions to wildlife diseases. Intensive interviews with key informants at each site served as the primary means of data collection (total n = 106). Qualitative analysis of the interview data revealed twenty factors that affected risk perceptions and reactions across cases. Although most of these factors reflected constructs identified previously in risk research as important influences on risk perceptions and reactions, at least three factors were novel: viewing a risk as (a) part of life, (b) ubiquitous, or (c) affecting quality of life independent of the direct effects of the risk object itself (e.g., through a disease vector). Most factors seemed to have consistent effects across cases on the types and magnitudes of risk perceptions and reactions. I summarize these patterns for each factor and discuss ways in which entities seeking to evaluate risk perceptions and reactions could potentially use this information. I then group the factors based on (a) the degree to which they were context specific versus more broadly applicable, (b) the degree to which they relate to objective constructs versus primarily mental constructs, and (c) whether they are tied principally to community attributes, individual attributes, or some combination of both. I describe how these groupings could facilitate risk communication. Finally, I place each of the identified factors under one of two broad themes: expectations and tangibility. I propose a framework based on these two themes as a parsimonious explanation of how several factors can work in concert to influence the types and magnitude of individuals' risk perceptions and reactions.