The authors discuss the problem associated with the severe, persistent course of drug-induced liver disease slightly responsive to traditional treatment in patients receiving antituberculous therapy. The objective of the study was to reveal the essence and causes of drug-induced liver damage characterized by its severe, persistent course, evident clinical and laboratory manifestations, and a weak response to traditional therapy and to develop diagnostic principles. The severe, persistent course of drug-induced liver disease slightly responsive to traditional therapy was shown to be caused by a few competitive pathological processes occurring in the liver rather than failures in the therapeutic and diagnostic process. Prognostic criteria for the severe, persistent course of drug-induced liver disease slightly responsive to traditional therapy have been developed. A diagnostic algorithm is proposed.