The fact that many infectious diseases are not effectively controlled with etiotropic drugs determines the relevance of a search for alternative methods, particularly those based on the modulation of immunity. The review analyzes rational approaches to the immunotherapy of infectious diseases, such as regulation of acquired immunity; correction of the quantitative and qualitative composition of the intestinal microbiota; and modulation of innate immunity. Among the drugs affecting the innate components of an immune response, the derivatives of muramyl dipeptide (MDP), a structural subunit of bacterial cell wall peptidoglycan, stand out in the context of a detailed study of the cellular and molecular mechanisms of action. The fact that it is expedient to clinically apply these immunomodulators in many diseases accompanied by inadequate infection control is beyond question. It is demonstrated that muramyl peptides (MP) may be also used to prevent excessive inflammatory responses. The adjuvant properties of MDP and its analogues can be employed for therapeutic vaccination. The data that the signals transmitted through NOD-like receptors (MP sensors) regulate intestinal homeostasis suggest that there is some potential for the use of MDP derivatives for the correction of dysbiosis and related immune disorders. Whatever the purpose of immunomodulation, the key to its effectiveness is to personalize the choice and regimens of immunotropic drugs.