The 5-HT6 receptor (5-HT6R) is one of the most recently discovered serotonin receptors and has received much attention after observations showing its procognition properties. Indeed, 5-HT6R appears to be a promising target to treat cognitive decline, particularly via its modulatory function of cholinergic and glutamatergic systems. 5-HT6Rs are present mostly in the central nervous system, in brain structures known to be particularly involved in memory. Growing evidence suggests that blockade of 5-HT6R can not only improve memory processes in adult rodents but also reverse age-related and pharmacologically induced deficits. 5-HT6R blockade could also have a beneficial effect on neuronal plasticity. Regarding these findings, several 5-HT6R antagonists are currently going through clinical trials. This review provides an overview of the major findings arguing in favour of a role for 5-HT6R antagonists in developing treatment for cognitive disorders related to ageing and neurodegenerative diseases.