Candida albicans and non-albicans series, the causative agents of vulvovaginal candidiasis, the most common infectious disease in gynecological practice, have a significant number of mechanisms to avoid the action of widely used groups of antifungal drugs. To treat vulvovaginal candidiasis with the increasing resistance of typical pathogens is an urgent problem in modern gynecology. Polyenes, including natamycin, exert their effects by directly blocking the synthesis of ergosterol, a vital component of the fungal cellular wall; as a result, the mechanisms of resistance are based precisely on changes in the structure of fungal sterols. When natamycin is used, as well as long, its resistance generally occurs less frequently and to a lesser extent than that of a number of other drugs widely used to treat vulvovaginal candidiasis, as evidenced by international and Russian studies. Conclusion: The absence of adverse reactions observed in most studies along with rapid symptom relief and long-term preservation of the achieved effect in women of different age groups, as well as pregnant women suggests that it is advisable to use natamycin to treat vulvovaginal candidiasis, including its chronically recurrent type that is characterized by a high risk pathogen resistance. © A group of authors, 2022.