Advances in technology have always had the potential and opportunity to shape the practice of medicine, and in no medical specialty has technology been more rapidly embraced and adopted than radiology. Machine learning and deep neural networks promise to transform the practice of medicine, and, in particular, the practice of diagnostic radiology. These technologies are evolving at a rapid pace due to innovations in computational hardware and novel neural network architectures. Several cutting-edge postprocessing analysis applications are actively being developed in the fields of thoracic and cardiovascular imaging, including applications for lesion detection and characterization, lung parenchymal characterization, coronary artery assessment, cardiac volumetry and function, and anatomic localization. Cardiothoracic and cardiovascular imaging lies at the technological forefront of radiology due to a confluence of technical advances. Enhanced equipment has enabled computed tomography and magnetic resonance imaging scanners that can safely capture images that freeze the motion of the heart to exquisitely delineate fine anatomic structures. Computing hardware developments have enabled an explosion in computational capabilities and in data storage. Progress in software and fluid mechanical models is enabling complex 3D and 4D reconstructions to not only visualize and assess the dynamic motion of the heart, but also quantify its blood flow and hemodynamics. And now, innovations in machine learning, particularly in the form of deep neural networks, are enabling us to leverage the increasingly massive data repositories that are prevalent in the field. Here, we discuss developments in machine learning techniques and deep neural networks to highlight their likely role in future radiologic practice, both in and outside of image interpretation and analysis. We discuss the concepts of validation, generalizability, and clinical utility, as they pertain to this and other new technologies, and we reflect upon the opportunities and challenges of bringing these into daily use.