Regulatory cells play a crucial role in the induction and maintenance of tolerance by controlling T cell as well as B and natural killer (NK) cell-mediated immunity. In transplantation, CD4⁺CD25⁺forkhead box P3⁺ T regulatory cells are instrumental in the maintenance of immunological tolerance, as are several other T cell subsets such as NK T cells, double negative CD3⁺ T cells, γδ T cells, interleukin-10-producing regulatory type 1 cells, transforming growth factor-β-producing T helper type 3 cells and CD8⁺CD28^- cells. However, not only T cells have immunosuppressive properties, as it is becoming increasingly clear that both T and non-T regulatory cells co-operate and form a network of cellular interactions controlling immune responses. Non-T regulatory cells include tolerogenic dendritic cells, plasmacytoid dendritic cells, mesenchymal stem cells, different types of stem cells, various types of alternatively activated macrophages and myeloid-derived suppressor cells. Here, we review the mechanism of action of these non-lymphoid regulatory cells as they relate to the induction or maintenance of tolerance in organ transplantation.