With the explosion of deep learning applications in medical imaging there is an urgent need to develop methods to evaluate the performance of artificial intelligence (AI) systems due to the increased complexities/varieties of AI technologies, the dependence of these new technologies on large datasets, and the emergence of novel types of clinical applications of AI systems. Proper testing methodology, metrics, appropriate training/tuning/validation study designs, and statistical analysis methods are needed to ensure that studies produce meaningful, robust, and generalizable results in a least burdensome fashion. These elements are key to the clinical adoption of AI technologies. Thus this Special Section for the Journal of Medical Imaging, Volume 7, Issue 1, encouraged relevant submissions in these topic areas. AI is not new to medical imaging. Since the earliest days of the SPIE Medical Imaging symposium there have been presentations on what was then referred to as Computer-Aided Diagnosis (CAD). The Computer-Aided Diagnosis conference at the larger SPIE Medical Imaging (MI) symposium was launched in 2006. Applications for CAD in mammography, lung CT, and chest x-ray imaging, all mature commercial products today, were discussed in their earliest phases at this conference. SPIE MI has also been the home for the introduction of new approaches to the assessment of CAD algorithms, a tradition that continues primarily through the conference on Image Perception, Observer Performance, and Technology Assessment. A perusal of the SPIE MI program through the years allows the reader to see the progression of AI algorithm development as well as methods for AI assessment. What is new to AI is the recent advance in computational power and the availability of large datasets that have enabled the successful application of deep neural network (DNN) architectures for various medical imaging tasks. These tasks include the common applications in the field related to the finding of suspicious areas in images for a reader to give a second-look, as well as the characterization of a reader's identified areas of suspicion with the support of AI. Newer tasks to which DNNs are being applied include image denoising, full image reconstruction from highly sparse or very noisy projections, triage systems that alert the user to high-priority cases so as to adjust casereading order, AI-selected image acquisition parameters on a per-patient basis, and the approximation of the ideal observer for use as a measure of image quality in complex imaging scenarios. For some applications, the performance of AI is being demonstrated to reach or surpass expert human performance such that automated diagnosis in which the clinician is replaced by the AI system is arguably close at hand. Moreover, the range of imaging modalities for which AI is being applied is vast, from the x-ray applications listed above, to optical, ultrasound, MRI, and digital pathology, the latter recently introduced as a conference track of its own at the SPIE MI symposium. Across the w...