Cognitive decline is considered a major public health concern and is growing in importance as the population ages. Progressive deterioration of cognitive function can lead to further impairment in day-to-day functioning. Cognitive decline is part of the normal aging process; it can also progress to Alzheimer’s Disease and Related Dementias (ADRD), for which there is no cure. Strategies to manage cognitive decline and ADRD include lifestyle interventions, behavioral interventions, and management of risk factors, including avoiding or minimizing the use of cognitive impairing medications. Many long-term care residents are admitted with cognitive decline and ADRD. These disorders and their associated symptoms may be treated with multiple medications, i.e., polypharmacy, which may result in adverse medication effects. This chapter will focus broadly on how medications may contribute to cognitive impairment as well as how medications are used to treat the behavioral and psychological symptoms of cognitive impairment. In particular, the widespread use of antipsychotics to control behavioral and psychological symptoms of ADRD has become a focus of many policy initiatives due to their limited evidence of effectiveness, adverse safety profile, and widespread use as a chemical restraint in long-term care facilities. This chapter also focuses on how the Center for Medicare & Medicaid Services has adopted and implemented strategies to reduce unnecessary antipsychotic medications, particularly in nursing homes.