In June 2021, the United States Food and Drug Administration (FDA) approved Biogen’s Aducanumab (brand name Aduhelm) as the first purported therapy to directly impact Alzheimer’s disease (AD) progression. While such a therapy was a long-awaited goal in AD treatment, Aduhelm’s approval quickly became controversial due to the fact that its approval was based upon the drug’s ability to clear protein aggregates rather than any observed clinical outcomes for patients. These aggregates had been established as a surrogate endpoint, a probable marker of future clinical outcomes, but the decision to do so was controversial. Furthermore, now that Aduhelm has been approved, considerations about the precedent set by these surrogate endpoint choices now have ramifications for future AD drugs, drugs for other neurodegenerative diseases, and the FDA’s Accelerated Approval Program. In this review, we introduce the concept of biomarkers for surrogate versus clinical endpoints, explain why surrogate endpoints are necessary for many diseases like AD, why the endpoints selected for Aduhelm were controversial, and discuss how more appropriate biomarkers can be chosen for future AD and Accelerated Approval drugs.