The article deals with the predominant representations of disease and its cause and treatment in the ancient tragic and comic drama in relation, on the one hand, to the magic-religious approach of Asclepius’ priesthood; and on the other, to the rational-scientific perception of Hippocrates’ followers, which was remarkably developed and disseminated during the fifth century B.C. It also traces the differently recorded representation of disease and treatment in the ancient tragedy and comedy and follows the escalation of medical syncretism and therapeutic optimism evident in dramatic literature: being literary introduced by Aeschylus’ Prometheus Bound and Sophocles’ Antigone, they are established by Euripides’ Alcestis and Sophocles’ Philoctetes, to be finally differentiated and prevalent in the plays of Aristophanes Wasps and Wealth, respectively. In the latter play, the last extant ancient comedy, the ambivalence of the classical thought has been remarkably portrayed.