© 2018, Springer Nature Switzerland AG. Purpose of Review: Pharmacologic immunosuppression is the mainstay of treatment for GVHD, but there is a crucial need for new therapeutic approaches. Our review focuses on the preclinical and clinical evidence supporting immune regulatory cell infusions, allograft engineering, and suicide-gene-transduced donor T cells to mitigate GVHD. We also review potential challenges to the adoption and use of these therapies. Recent Findings: Mesenchymal stromal cells and regulatory T cells appear effective in preventing and treating GVHD in preliminary studies, although methods of isolating and expanding these cells differ and warrant further investigation. Elimination of naïve or host-reactive donor T cells from allografts can prevent GVHD but may increase infection risk. Donor T cells engineered with human caspase 9 are rapidly eliminated after inducible gene activation, preventing GVHD. Summary: Cellular therapeutics are a promising approach to mitigate GVHD. Clinical trials are underway domestically and internationally to establish the safety and efficacy of these approaches.