Drug repurposing is the method of discovering new therapeutic indications for previously available drugs. It is increasingly appealing to repurpose existing drugs for the treatment of rare and common diseases due to high attrition rates, high costs, and the slower rate of drug discovery and development. The concept of drug repurposing may not be new, but it has gained momentum over the past few years. Several drugs have been effectively repurposed. Over the past decade, numerous pharmaceutical companies have developed new drugs based on the identification of novel biological targets using drug repurposing. This process combines experimental and in silico techniques to rationally develop/identify new applications for pharmacological compounds. However, the prospects of this strategy have not been fully utilized, owing in part to regulatory, technological, and legal challenges. Many promising drugs are shelved because of inadequate efficacy, poor market potential, and consolidation in the industry. In this chapter, we have discussed these challenges. Various innovative strategies that could address and solve these barriers, realizing the full potential of drug repurposing, have also been discussed.