Women have a significantly higher risk of developing Alzheimer's disease (AD) than men. This has contributed to the hypothesis that the menopause may contribute to the cascade of pathological processes leading to AD. Studies into the role of oestrogen therapy (OT) on the prevention and treatment of AD have led to equivocal findings. In summary, these studies have suggested that OT may protect against AD if it is given to younger women around the time of the menopause (the 'critical period' hypothesis). However, it may have a negative or neutral effect if it is prescribed to women after this time. This chapter will discuss some of the putative biological mechanisms that may underlie these effects.