The serotonin 6 receptor is attracting attention as an etiological contributor in cognition deficits in diseases such as Alzheimer's disease, anxiety/depression and schizophrenia. In this review, we discuss the role of this recently discovered G protein-coupled receptor in cognition and memory, particularly in Alzheimer's disease. A surge in publications that describe the development of ligands for this receptor have recently come to light, underscoring the emerging interest in this receptor as a drug target. We also explore the current status of structure-activity relationship studies that have focused on the design of novel antagonists for the serotonin 6 receptor.