Design of multi-target directed ligand (MTDL) is believed to be a novel and improved approach for diseases that elucidate a multifactorial nature. Alzheimer’s disease (AD) is related to increased levels of the amyloid β peptide (Aβ), the hyperphosphorylated tau protein, free radicals, oxidized proteins and lipids, metal ion dysregulation and many more. For the multifactorial aetiology of AD and the fact that till date there is no effective treatment besides drugs alleviating associated symptoms, molecules designed to hit simultaneously different key targets of the complex pathological network emerges as a more realistic alternative. In this context, the present chapter puts forward a note of several strategies adopted for the development of MTDLs for the disease followed by a case study leading to in vitro validation. © 2018, Springer Science+Business Media New York.