This essay addresses a question that, I suggest, is implicit in Franz Kafka’s novella Metamorphosis: How can we defend individuals’ humanity when prolonged illness or other misfortune appears to have changed them utterly and when they themselves lack the full capacity to make their claim? I review critical commentaries on Metamorphosis and then discuss the protagonist’s misfortune and his family’s response to it as a “worst-case scenario” for ill persons and their caregivers—the potential that, over time, those who care for the ill may become increasingly unable to empathize with them or honor their humanity in attitude and deed. I draw on personal experience to portray this problem as a crisis in the relationship between ill persons and their caregivers and to demonstrate professional, institutional, and personal practices that arise to counter potential dehumanization of the ill person. The awareness of the potential for moral exhaustion, the effort to represent and voice memories of the ill person, and the capacity to bear witness to his or her suffering are particularly powerful means to preserve humanity in the face of grave illness. Throughout, I consider the interactions between the work of art and lived experience and the ways they can inform each other.