Compared with traditional de novo drug discovery, drug repurposing has become an attractive drug discovery strategy due to its low-cost and high efficiency. Through a comprehensive analysis of the candidates that have been identified with drug repositioning potentials, it is found that although some drugs do not show obvious advantages in the original indications, they may exert more obvious effects in other diseases. In addition, some drugs have a synergistic effect to exert better clinical efficacy if used in combination. Particularly, it has been confirmed that drug repositioning has benefits and values on the current public health emergency such as the COVID-19 pandemic, which proved the great potential of drug repositioning. In this review, we systematically reviewed a series of representative drugs that have been repositioned for different diseases and illustrated successful cases in each disease. Especially, the mechanism of action for the representative drugs in new indications were explicitly explored for each disease, we hope this review can provide important insights for follow-up research.