Despite negative topline phase 3 clinical trial results for bapineuzumab and solanezumab in mild to moderate AD, findings from these trials and recent advances suggest renewed optimism for anti-amyloid therapies. Aβ immunotherapy has now demonstrated its ability to engage CNS Aβ and modify downstream CNS biomarkers in bapineuzumab treated patients, and to show likely cognitive benefits in mild patients treated with solanezumab. The current availability of potent BACE inhibitors provides additional opportunities to test the value of reducing Aβ in the clinic. Trial enhancements, such as selecting and enriching for early stage AD, treating participants longer and using more sensitive composite endpoints may further improve our chances of demonstrating clinical efficacy and securing beneficial treatments for patients.