Individuals with chronic autoimmune disease experience a sense of vulnerability. In part, this relates to the struggle for finding the meaning of the illness. The consequent existential distress may manifest in an unseated sense of personhood. Insight into the mechanism of this state of powerlessness and of perceived loss of agency is central to establishing a supportive clinician–patient relationship. This present exposition underscores the concept of autoimmunity as one that represents a demarcation in the psyche: one that is not just a threat to our sense of self-hood but also to our humanity. Autoimmunity exposes the challenge imposed on the relating of the self to one’s own self and hence is an ontological challenge. The breach of the boundary between self and not-self that is caused by the autoimmune process culminates in feelings of alienation.