Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease and a drug which targets a single protein will not provide a cure for the disease. Currently available drugs for AD are all palliative rather than curative. FDA approved only five drugs for the treatment of AD, which includes tacrine, donepezil, galantamine, rivastigmine, and memantine. Tacrine discontinued due to its hepatotoxicity. The lack of therapeutic effectiveness of the single-target drugs and multifactorial etiology of AD leads to the design of multitarget directed ligands for AD. Objective: The researchers in this field are constantly putting effort for the development of a drug for the exact cure of this disease by exploring the different biological targets associated with AD. The present review comprises various multitarget approaches and tools used for finding out a lead compound or a new drug, which will give a cure for AD. Methods: We have scrutinized and reviewed 75 research articles published in various peer reviewed journals in the last two decades in the field of multi target directed ligand approaches for the discovery of a new therapeutic agent for AD. Results: The review highlights the recent advances in the field of AD research and showed that still the battle for the discovery of an effective drug for AD is in process and AD still remains an incurable disease for which treatment is just palliative. Conclusion: The review might be helpful for researchers working on multi target directed ligands against AD.

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