Restenosis is a pathophysiological phenomenon that can occur in patients submitted to revascularization procedures (bypass, endarterectomy, angioplasty), possibly resulting in new narrowing of injured vessels. Vascular restenosis remains a pressing clinical problem, despite the therapeutic strategies and devices developed so far. Stem cells hold a great potential for the regeneration of damaged tissues in cardiovascular diseases. Recent studies clearly indicated that different stem cell populations contribute to vascular remodeling after injury. Nevertheless, the exact role of vascular cell precursors in restenosis pathophysiology is not yet well defined, as heterogeneous and contrasting data are currently available. Mesenchymal stromal/stem cells (MSCs) are non-hematopoietic multi-potent stem-like cells able of differentiating into both mesenchymal and non-mesenchymal lineages. MSCs offer a series of advantages: a) they can be isolated from a small aspirate of bone marrow; b) extensively proliferate in vitro while preserving a normal karyotype and telomerase activity on several passages; c) express low immunogenicity and hence their use should not require a pharmacological immunosuppression. MSCs have an intrinsic ability to differentiate into functional cell types able to repair the diseased or injured tissue in which they are localised. For this reason, MSCs are currently under scrutiny for treatment of different cardiovascular diseases. Nevertheless, it has not yet been clearly determined whether MSCs can substantially contribute to a positive resolution of restenosis after vascular injury. This review will provide information about the mechanisms at the basis of vascular restenosis and the current knowledge of the role, positive or negative, played by MSCs in restenosis progression as highlighted by recent experimental protocols.