Drug repositioning offers an innovative approach to drug discovery with great potential in the field of Alzheimer’s Disease and dementia therapeutics. Investigation of licensed compounds enables processing through the drug discovery pipeline in a rapid and cost-effective manner. A growing body of evidence supports the translation of priority compounds to be taken forward to clinical trials, based on established and proposed mechanisms of action. A number of drugs have already entered clinical trial following repositioning, and novel technologies have been created to enable high-throughput screening. This review discusses the novel approaches that build on transcriptional signature profiling to support repositioning in AD, and the novel candidate drugs that are emerging from this exciting new technique.