Smooth muscle cell proliferation plays a major role in the genesis of restenosis after angioplasty or vascular injury. Local delivery of agents capable of modulating vascular responses, have the potential to prevent restenosis. However, the development of injectable microspheres for sustained delivery to the arterial wall is a major challenge. We have been investigating biodegradable micro/nanospheres for the local intra-arterial drug delivery. This review is dedicated to the use of poly lactic acid (PLA) and copolymers of lactic acid and glycolic acid (PLGA) for drug encapsulation and their targeted delivery. We have emphasized the use of surface coatings for improving the stability and controlled drug release of PLA based microspheres. Finally, a discussion is included of anticancer agents that may impact vascular restenosis such as taxol, cisplatin and colchicines.