Drug resistance is a serious issue that compromises the efficacy of many drugs and antibiotics.  One mechanism underlying the development of resistance is the alternation in the target enzyme or receptor resulting in gradual silencing of the target to the effects of the ligands.  Basak et al developed a method called differential QSAR (DiffQSAR) whereby test data of drugs on their effects on the sensitive and resistant targets are used to characterize the phenomenon of drug resistance using mathematical molecular descriptors.  This paper will summarize our research in this area.