Eosinophils are granulocytes typically associated with immune responses to a limited number of specific insults, including helminth infection and exposure to various allergens. Moreover, the overwhelming consensus from the literature is that eosinophils evolved as uniquely destructive leukocytes with cytotoxic activities as an adaptation for host defense. However, recent studies now suggest that the parochial caricature of eosinophils as effector cells with nonspecific killing abilities that evolved as a host defense mechanism against large nonphagotizable parasites is incomplete. A new paradigm has emerged describing eosinophils as initial responders to cell death/tissue damage that are a part of remodeling/repair processes and, more importantly, significant contributors to localized innate and acquired immune responses as well as systemic adaptive immunity. Significantly, this new paradigm does not preclude roles for eosinophils in host defense leading to tissue damage but instead suggests the equal importance of eosinophil-associated regulatory mechanisms modulating local tissue immune responses. The goal of this review is to summarize the data in support of this new paradigm. In turn, we believe that this expanded role provides a probable explanation for the presence of eosinophils in diverse disease settings such as asthma, allergy, cancer, transplant rejection, gastrointestinal inflammation, and viral or helminth infection.