A recent EU/US CTAD Task Force Report focused on non-amyloid approaches to Alzheimer’s disease (AD) modification (1). While the broad range of targets and therapies highlighted is in some ways sobering, several themes and advances in the field point to principles and technologies that are encouraging and will likely accelerate progress. These themes include: the view that amyloid and non-amyloid approaches might ultimately be complementary or synergistic; the biological diversity of approaches; emerging -omics strategies that might help guide such options; and finally, the incorporation of aging biology into perspectives of target prioritization and disease modification.