Drug eluting stents (DES) have significantly reduced restenosis when compared to BMS and are considered the standard of care in the treatment of symptomatic coronary artery disease. However, late stent thrombosis has emerged as a major concern with the use of first generation DES. Pathologic studies of patients dying from late DES thrombosis (first generation sirolimus-eluting stents and paclitaxel-eluting stents) showed that DES are associated with delayed healing characterized by poor endothelialization of stent struts and persistence of fibrin as compared to BMS. Additional risk factors for LST include long lesions, left main coronary artery, bifurcation stenting, ruptured plaques, and hypersensitivity reactions. Currently, the next generation DES are being developed to optimize the three major components of DES: the stent platform, the polymer coating and the drug. New technologies include biodegradable polymers and stents, polymer free drug delivery and prohealing approaches. Further preclinical testing and evaluation through large clinical trials are needed to determine the safety and efficacy of future DES in clinical practice.