Memantine, a non-competitive NMDA antagonist, has been clinically used in the treatment of dementia in Germany for over ten years. The rationale for this indication is strongly related to the physiological and to the pathological role of glutamate in neurotransmission. Physiolgically, NMDA receptors mediate synaptic plasticity by acting as a coincidence detector. Only those synapses that show temporally and spatially discrete activation of NMDA receptors undergo plastic changes secondary to Ca++ influx after rapid unblocking of Mg++, thus crucially contributing to memory and learning processes. The voltage-dependency of Mg++ is so pronounced that under pathological conditions it leaves the NMDA channel upon moderate depolarisation, thus interrupting memory and learning. Its pharmacological properties allow memantine to rapidly leave the NMDA channel upon transient physiological activation by synaptic glutamate (restoring significant signal transmission), but to block the sustained activation of low glutamate concentration under pathological conditions, i. e. to protect against excitotoxicity as a pathomechanism of neurodegenerative disorders. Memantine acts as a neuroprotective agent in various animal models based on both neurodegnerative and vascular processes as it ameliorates cognitive and memory deficits. Memantine has shown to be effective and safe in the treatment of dementia, particularly Alzheimers disease, in controlled clinical trials. Provided that the dose is slowly increased it is generally well tolerated and safe up to 20 and 30 mg per day, with intake preferably in the morning. The compound is completely absorbed after oral intake with Cmax values after 6 hours, undergoes little metabolism and has a terminal elimination half life between 60 and 100 hours. Due to its low potential of interaction, memantine can be combined with acetylcholinesterase inhibitors, the mainstay of current symptomatic treatment of Alzheimers disease and it is suited in elderly patients receiving multiple drug therapy.