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Innovative ICT technologies, approaches, and applications are becoming increasingly pervasive in medicine and healthcare. At the same time, physicians and medical professionals are adopting and exploiting these complex and advanced systems based on the latest technologies for their daily routine. Scientific research constantly proposes new approaches and applications with high potential for use in the e-health sector. Therefore, it is necessary to disseminate these new results and enhancements in this area to take full advantage of the latest advances in ICT applied to the medical sector. This Special Issue presents innovative e-health approaches and applications that exploit the most recent ICT technologies and techniques, such as artificial intelligence, the Internet of Medical Things, and others, to implement smart tools and methodologies to support the work of physicians and promote the adoption of new e-health tools in medicine and by healthcare organizations. Moreover, the contributions included in the Special Issue address the issues that usually affect this domain, such as data privacy, cyber security of the devices and healthcare infrastructures, awareness, and the involvement of medical personnel.