Book excerpt: Increasing interest in the development and validation of quantitative imaging biomarkers for oncologic imaging has in recent years inspired a surge in the field of artificial intelligence and machine learning. Initial results showed promise in identifying potential markers of treatment response, malignant potential, and prognostic predictors, among others; however, while many of these early algorithms showed the optimistic ability to separate pathologic states on “in-house” datasets, it was often the case that these classifiers generalized poorly on external validation sets and thus were of limited utility in the clinical setting. This issue was additionally compounded by the frequent use of data filtering and feature selection techniques in many studies to further bolster the machine learning results in limited case scenarios, thereby biasing the overall fit and further reducing generalizability.