The driver-based chronic disease model is a novel construct that integrates key mechanistic drivers, distinct intuitive staged progression over time, and both biological and non-biological determinants that initiate and impel the natural history. This dynamic but simple heuristic can serve as a guide for research, education, and clinical practice and can be enriched/modified as new information becomes available. Many research gaps remain, and as they are closed, the performance of these models can be expected to improve and become more widely accepted.