Drug repositioning is an important component of therapeutic stratification in the precision medicine paradigm. Molecular profiling and more sophisticated analysis of longitudinal clinical data are refining definitions of human diseases, creating needs and opportunities to re-target or reposition approved drugs for alternative indications. Drug repositioning studies have demonstrated success in complex diseases requiring improved therapeutic interventions as well as orphan diseases without any

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... own treatments. An increasing collection of available computational and experimental methods that leverage molecular and clinical data enable diverse drug repositioning strategies. Integration of translational bioinformatics resources, statistical methods, chemoinformatics tools and experimental techniques (including medicinal chemistry techniques) can enable the rapid application of drug repositioning on an increasingly broad scale. Efficient tools are now available for systematic drug-repositioning methods using large repositories of compounds with biological activities. Medicinal chemists along with other translational researchers can play a key role in various aspects of drug repositioning. In this review article, we briefly summarize the history of drug repositioning, explain concepts behind drug repositioning methods, discuss recent computational and experimental advances and highlight available open access resources for effective drug repositioning investigations. We also discuss recent approaches in utilizing electronic health record for outcome assessment of drug repositioning and future avenues of drug repositioning in the light of targeting disease comorbidities, underserved patient communities, individualized medicine and socioeconomic impact.