Recently, the substantial progress has been made toward understanding the human microbiota as an ecosystem that functions as a separate organ in a macro-organism. More and more data on the microbiome as the aggregate of microorganism genes that reside on or within the human body appear. Deterioration of the environment, changes in food production technologies, widespread use of antibiotics result in serious human microbiota disorders, most often in the form of gut dysbiosis of varying severity. The investigation into the causes and the correct choice of a probiotic containing the identified microorganisms with the indication of genus, species, strain and their quantitative composition is the criterion for the success of dysbiosis therapy. The purpose of this article is to discuss the criteria for rational probiotic therapy and prevention of gut dysbiosis and associated diseases. It should be considered that the treatment of diseases accompanied by dysbiosis should be comprehensive and include the elimination of the cause of the disease, the correction of nutrition, the elimination of pathogenic agents and their toxins in the gastrointestinal tract, as well as the restoration of the microbiota composition and functional activity. Probiotics play an important role in restoring the composition and functional activity of microbiota. According to the current guidelines of the World Gastroenterological Organization (WGO), a certain quantity of bacteria (KOE of microorganisms) that is necessary to achieve a  positive effect is an important criterion for the efficacy of probiotic drugs.