Mesenchymal stem cells (MSCs) have a vastly unharnessed therapeutic potential with close to 400 studies currently registered on clinicaltrials.gov for evaluation of their clinical promises. While many of these investigations are for immune‐mediated disorders, there is no established consensus on how to optimize the immunomodulatory properties of MSCs. Factors that could be used to predict efficacy of MSC therapies include donor heterogeneity, recipient environment and drug interactions. Incorporating pertinent quality control parameters to maximize the clinical potential of MSCs through good manufacturing practice (GMP) production of clinical grade cells could lead to the realization of greater therapeutic success.