It is known that high cholesterol is associated with cardiovascular disease. Cholesterol also regulates the production of the toxic amyloid beta (Aβ) peptide in Alzheimer’s disease (AD). Therapies already developed or in development for dyslipidemia and atherosclerosis are becoming attractive for reducing Aβ in the brains of patients affected by AD. We have previously reported that drugs specifically targeting one step of the cholesterol pathway, acyl-coenzyme A: cholesterol acyltransferase (ACAT) inhibitors, reduced generation of toxic Aβ peptide in cells and an animal model of AD. While currently not marketed, ACAT inhibitors are available for testing in animal models and clinical trials against AD. Our work in these studies, including the design and development of novel ACAT inhibitors, should result in one or more novel ACAT inhibitors with the potential to prevent and treat AD.