In 2021, aducanumab, an immunotherapy targeting amyloid-β, was approved for Alzheimer's disease (AD) by the US Food and Drug Administration thanks to positive results on a putative biological surrogate marker. This approval has raised an unprecedented controversy. It was followed by a refusal of the European Medicine Agency, which does not allow the marketing of drugs solely on biological arguments and raised safety issues, and important US coverage limitations by the Centers for Medicare & Medicaid Services. Two other anti-amyloid immunotherapies showed significant results regarding a clinical outcome in phase II trials, and five drugs are being studied in phase III trials. Lecanemab is currently under examination for an ‘Accelerated Approval’ in the US, with an expected decision in January 2023. The common feature and novelty of these anti-amyloid immunotherapies, compared to those tested in previous trials of the 2010s, is their ability to induce a high clearance of amyloid load, as measured with positron emission tomography, in the brain of early-stage biomarker-proven AD patients. In the first part of this review, we underlined through a meta-analysis that the pooled data from high-clearance anti-amyloid immunotherapies trials demonstrated a significant but slight clinical effect after 18 months. Still, safety remains an issue with serious and symptomatic amyloid-related imaging abnormalities, which are seldom (∼1 per 200 treated patients) but occur beyond chance. In the second part of this review, we hypothesized that there is a high probability that some phase III trials of high-clearance anti-amyloid immunotherapies in early AD will finally be unarguably positive on clinical outcomes in the next five years with acceptable safety data. This may, in turn, lead to approval by the European Medicine Agency if the risk-benefit profile is deemed favorable. Such approval would be a game-changer in managing AD patients and for the organization of memory clinics in France. We review the possible timeline and scenarios for putative approval in France and make propositions regarding putative use in clinical practice, putative implementation in a real-life setting, and ethical considerations.