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This article builds a broad theory to explain how people respond, both biologically and behaviorally, when targeted with incivility in organizations. Central to our theorizing is a multifaceted framework that yields four quadrants of target response: reciprocation, retreat, relationship repair, and recruitment of support. We advance the novel argument that these behaviors not only stem from biological change within the body but also stimulate such change. Behavioral responses that revolve around affiliation and produce positive social connections are most likely to bring biological benefits. However, social and cultural features of an organization can stand in the way of affiliation, especially for employees holding marginalized identities. When incivility persists over time and employees lack access to the resources needed to recover, we theorize, downstream consequences can include harms to their physical health. Like other aspects of organizational life, this biobehavioral theory of incivility response is anything but simple. But it may help explain how seemingly “small” insults can sometimes have large effects, ultimately undermining workforce well-being. It may also suggest novel sites for incivility intervention, focusing on the relational and inclusive side of work. The overarching goal of this article is to motivate new science on workplace incivility, new knowledge, and ultimately, new solutions.