Neurodegenerative disorders have a devastating disease course and an increasing prevalence due to prolonged life expectancy. In the last decades, it has become increasingly clear that these diseases often start much earlier, before the onset of symptoms, creating a potential window for pre-symptomatic treatment, a strategy that is desirable from both the biologic and the ethical point of view. However, studying treatments for a pre-symptomatic population presents objective difficulties. This article intends to give a perspective about opportunities and challenges of pre-symptomatic prevention of neurodegenerative diseases. Besides the requirement for biomarkers that would facilitate both the selection of study population and demonstrating a treatment effect, further considerations about balancing benefits, risks and uncertainties pertaining a pre-symptomatic population will be examined.