Alzheimers disease is a complex neurodegenerative disorder with a multifaceted pathogenesis. This fact has long halted the development of effective anti-Alzheimer drugs. Recently, however, basis for a therapeutic strategy based on multi-target-directed ligands has been formed. In this context, dual binding site acetylcholinesterase inhibitors represent a suitable starting point. The rational modification of their structures to provide them with additional biological properties has emerged as a successful approach.