Drug repurposing is a powerful technique which has been recently employed in both industry and academia to discover and validate previously approved drugs for new indications. It provides the quickest possible transition from bench to bedside. In essence, computational strategies are appealing because they putatively nominate the most encouraging candidate for a given indication. A wide range of computational methods exist for repositioning. In this chapter we present the guidelines for performing integrated drug repurposing strategy by combining disease-disease association and molecular simulation analysis. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.