Ischemic diseases refer to a wide range of diseases caused by reduced blood flow and a subsequently deficient oxygen and nutrient supply. The pathogenesis of ischemia is multifaceted and primarily involves inflammation, oxidative stress and an apoptotic response. Over the last decade, mesenchymal stem cells (MSCs) have been widely studied as potential cell therapy agents for ischemic diseases due to their multiple favourable functions. However, the low homing and survival rates of transplanted cells have been concerns limiting for their clinical application. Recently, increasing studies have attempted to enhance the efficacy of MSCs by various strategies including genetic modification, pretreatment, combined application and biomaterial application. The purpose of this review is to summarize these creative strategies and the progress in basic and preclinical studies.