Multipotential mesenchymal stromal cells (MMSCs) are the subject of increasing scientific interest due to their key role in physiological renewal and repair. Allogeneic MMSCs interaction with other components of tissue environment, in particular with immune cells, represent one of the most intriguing question of modern cell physiology. MMSCs possess pronounced immunomodulatory capabilities based on their "immmunopriveledge" properties and the ability to suppress immune response. This review is highlighted the current state of art in the field of MMSCs immunomodulatory effects realization and mechanisms. MMSCs and immune cells interaction represents complex multidirectional process governed by both direct cell-to-cell interactions and soluble factors (interferon-gamma, tumor necrosis factor, prostaglandin E2, hepatocyte growth factor, interleukins ets.). The importance of physical environmental factors, primarily oxygen tension, on peculiarities of MMSCs and immune cells interaction is discussed.