Mesenchymal stem or stromal cells (MSC) are considered a promising new therapeutic strategy for the treatment of several pathological conditions. Due to their immunomodulatory properties, they are currently employed in clinical trials aimed at preventing or treating steroid-resistant acute graft-versus-host disease (GvHD), a frequent complication of allogeneic hematopoietic stem cell transplantation (HSCT). In addition, the use of MSC has been proposed for the treatment of autoimmune diseases. A number of recent studies have focused on the influence of MSC on dendritic cell (DC) function. DCs play a critical role in initiating and regulating immune responses by promoting antigen-specific T cell activation. Moreover, they are involved in efficient cross-talk with different cells of the innate immune system. DC are the most effective antigen-presenting cells and prime naïve T cells to initiate adaptive immune responses including those against allogeneic cells or self-antigens. Thus, alteration of DC generation or function may greatly contribute to the inhibition of T cell responses. In this context, MSC were shown to interfere with DC maturation from monocytes or CD34(+) hemopoietic precursors thus further confirming their role in immune regulation and their usefulness in cell-based therapies.