Drug combination therapy increases successful drug repositioning

•Publications for drug repositioning have drastically increased in past five years.•Different types of drug repositioning and available resources have been summarized.•Drug combination increases the success rate of drug repurposing screens.

Repositioning of approved drugs has recently gained new momentum for rapid identification and development of new therapeutics for diseases that lack effective drug treatment. Reported repurposing screens have increased dramatically in number in the past five years. However, many newly identified compounds have low potency; this limits their immediate clinical applications because the known, tolerated plasma drug concentrations are lower than the required therapeutic drug concentrations. Drug combinations of two or more compounds with different mechanisms of action are an alternative approach to increase the success rate of drug repositioning.