Alzheimer's disease (AD) is a progressive multifactorial neurodegenerative disorder. Currently, no effective treatment is available and this is due to multiple factors involved in pathophysiology and severity of AD. A recent approach for the rational design of new drug candidates, also called multitarget-directed ligands (MTDL) strategy, has been used to develop a variety of hybrid compounds capable to act simultaneously in diverse biological targets. The discovery of drug candidates capable of targeting multiple factors involved in AD pathogenesis would greatly facilitate in improving therapeutic strategies. This review is a complement to another review article, recently published by our group, which covered the previous period of 2005-2012, and highlights recent advances and examples of the exploitation of MTDLs approach in the rational design of novel drug candidate prototypes for the treatment of AD.