Salaudeen et al. review common reliability failures in predictive and generative AI for healthcare, including erroneous model outputs, clinically unjustified performance differences, and deployment-time degradation. They examine why existing technical solutions fall short and argue for lifecycle-aware evaluation, continuous monitoring, and institutional governance.

(Cell 188, 6953–6970.e1–e8; November 26, 2025)

Drawing inspiration from Hilbert’s list of 23 mathematical problems that have focused the mathematical community’s attention for more than a century, we propose fifteen grand AI challenges to focus the biomedical community’s attention on critically relevant questions, most of which still lack effective predictive methodologies.