The resistance of microorganisms to antimicrobial drugs is an important problem of medicine. The aim – to study forming of the resistance to decamethoxine® (DCM®), decaminum (DC) and properties of microorganisms. In the study, a quantitative assessment of antimicrobial drugs was performed based on the activity index of the drug (AID), which shows the ratio of the working concentration of antiseptic to its minimum active concentration for a specific agent. The first indicator for determining the AID is derived from the instructions for the use of the drug, the relevant directories. Minimum inactivation concentration (MIC) values was determined experimentally in strains of the corresponding species that did not have contact with medicinal products. Microbiological studies on diphtheria rods, Staphylococcus albus and S. aureus, clinical strains of Candida albicans, which possessed typical tinctorial, morphologic, and cultural properties were carried out in this work. The effective concentrations of medicinal antimicrobial drugs decamethoxine®, decaminum, levorinum, nystatin were determined by means of the method of double serial dilutions. Conditions were defined for the formation of resistant forms of microorganisms (nutrient medium, microbial load, concentration of drugs). There was analyzed the resistance of Staphylococci, Corynebacterium diphtheria, Candida albicans drugs and the monitoring of the resistance of microorganisms to decamethoxine®, decaminum, levorinum, nystatin was carried out. According to the results of experimental study on the nutrient medium the slow forming of resistance in Staphylococci, C.diphtheria, C.albicans to DCM and DC were found. These studies showed a lack of cross-resistance of clinical strains of C.albicans to antimycotics DCM® and DC, on the one hand, and levorinum and nystatin on the other. Resistant to DCM of C.albicans were found to be susceptible to decaminum (3,9 μg/ml), levorinum (0,12 μg/ml) and nystatin (1,9 μg/ml). While forming the resistance to antimicrobial drugs changes of morphology with the formation of polymorphic cells have been established in microorganisms. The loss of biological activity of microorganisms due to changes in the activity of microbial cell enzymes during the formation of resistance was determined. The expediency of using DCM®, decaminum, levorinum, nystatin for prevention, treatment, overcoming of resistance in resistant variants of microorganisms to DCM®, decaminum.