As a book of critical theory, Sontag's Illness as Metaphor is not a character-based book. Rather, it explores the ways in which Western society has used physical illnesses (especially tuberculosis and cancer) as metaphors to address social issues.

Most pointed in her study is the exploration of TB as a romantic disease that prescribed removal to mountain sanatoriums, and elegant portrayals of characters too refined for this world, wasting away in piteous but creative exile (think Keats). Cancer, on the other hand, labored under Freudian ideas of repression and the "cancer temperament" (think Auden's Miss Gee). When society uses these false understandings of a medical condition and applies the metaphor to social issues, pernicious consequences become common.

Sontag discusses how early Nazi rhetoric described Jews in the metaphor of TB, constructing a solution based on exile. When the rhetoric associated Jews as a cancer on society, extermination and other violent means became thinkable.

Various writers and historical figures are mentioned in this small treatise, but the main character with real agency is the cultural "mind" that constructs, disseminates, and re-enforces these metaphors that make possible the otherwise unthinkable. By suggesting that temperament or passion seeps into the cells of the afflicted, society burdens both the ill and society with metaphorical overlaps that ultimately are more harmful to all as a way of giving meaning or structure to experiences that are poorly understood.