Alzheimers disease (AD) is one of the major neurodegenerative diseases that deteriorates cognitive functions and primarily affects associated brain regions involved in learning and memory such as the neocortex and the hippocampus.Following the discovery and establishment of its role as a neurotransmitter, serotonin (5-HT), was found to be involved in a multitude of neurophysiological processes including mnesic function through its dedicated pathways and interaction with cholinergic, glutamatergic, GABAergic and dopaminergic transmission systems.Abnormal 5-HT neurotransmission contributes to the deterioration of cognitive processes in AD and other neuropathologies including schizophrenia, stress, mood disorders, depression and normal ageing.Numerous studies have confirmed the pathophysiological role of 5-HT system in AD and several drugs enhancing 5-HT neurotransmission are effective in treating the AD-related cognitive and behavioural deficits.Here we will briefly discuss its role in higher brain function and provide in depth account of the pathological modifications of serotonergic transmission in AD that we have recently discovered, as well as some new developments in which we have demonstrated that manipulation of 5-HT serotonin synthesis pathway can significantly reduce some of the disease pathological burdens;bringing new insights to further and/or complimentary therapeutical approaches.