Alzheimer's disease (AD), the most common cause of dementia, is a progressive neurodegenerative disorder affecting millions of people worldwide. AD has a multifactorial origin, resulting from an interaction between genetic susceptibility and environmental risk factors. Genetic, epidemiological, experimental and clinical data strongly suggest that the metabolism of cholesterol has an important role in AD pathogenesis. Several studies have demonstrated that high concentrations of serum cholesterol increase the risk of AD. Statins, drugs that reduce cholesterol levels, have been investigated as a possible treatment for AD. However, the literature is not exempt of contradictory results. In this article, we review a recent article by Reitz et al. demonstrating that higher levels of high-density lipoprotein cholesterol, total cholesterol and non-high-density lipoprotein cholesterol are associated with lower risk of AD. In addition, we discuss the current state of knowledge regarding the relationship between plasma cholesterol and AD, stressing the need for understanding the molecular mechanisms behind this association.