Mesenchymal stem or stromal cells (MSCs) are easily isolated from bone marrow or fat tissue and their potential of multilineage differentiation has initially led to the development of strategies for tissue engineering applications. More recently, they have gained much interest based on their trophic and immunomodulatory properties that have stimulated their evaluation in various clinical trials aiming at modulating the host immune response in graft-versus-host disease or autoimmune diseases. The clinical applications of MSCs for rheumatic diseases are limited and address primarily their potential to help tissue repair/regeneration. The aim of the present review is to focus on the mechanisms by which MSCs might exhibit a therapeutic potential in rheumatology and present the current data on the undergoing clinical trials. Special attention is given to miRNA expression in rheumatic pathologies and their possible modulation for future innovative strategies as biomarkers or therapeutic targets.