The focus of this review is to: 1) describe our understanding of insulin resistance in the brain and how it relates to, and differs from, peripheral insulin resistance, 2) describe in detail the contributors to BIR, including the role of the insulin receptor (INSR) particularly in the brain, 3) highlight current tools to study BIR, 5) elucidate how BIR may correlate with hallmarks of AD pathology underlying cognitive impairment and decline, and dementia, and 6) define where insulin resistance occurs within the brain and in individual cell types. The gene discussed is INS; the disease is Insulin resistance.