Diabetes mellitus is associated with cognitive dysfunction and abnormalities that can be seen with brain imaging. Recent studies provide important new insights into the nature and severity of these cerebral complications that help to explain why some patients with diabetes have clinically relevant neurocognitive morbidity, whereas most are apparently unaffected. This Personal View investigates the hypothesis that clinically relevant diabetes-related cognitive decrements mainly occur at two crucial periods in life: when the brain is developing in childhood, and when the brain undergoes neurodegenerative changes associated with ageing. Outside of these periods cognitive decrements mainly occur in patients with notable diabetes-related comorbidities, in particular microvascular or macrovascular complications. The identification of crucial periods and conditions for the development of diabetes-related cognitive decrements helps to draw the attention of physicians to individuals at risk and can direct future studies into the mechanisms that underlie these conditions.