Modern medicine, both in clinical practice and research, has become more and more based on data, which is changing equally in type and quality with the advent and development of healthcare digitalization. The first part of the present paper aims to present the steps through which data, and subsequently clinical and research practice, have evolved from paper-based to digital, proposing a possible future of this digitalization in terms of potential applications and integration of digital tools in medical practice. Noting that digitalization is no more a possible future, but a concrete reality, there is a strong need for a new definition of evidence-based medicine, which must take into account the progressive integration of artificial intelligence (AI) in all decision-making processes. So, leaving behind the traditional research concept of human intelligence versus AI, poorly adaptable to real-world clinical practice, a Human and AI hybrid model, seen as a deep integration of AI and human thinking, is proposed as a new healthcare governance system. The second part of our review is focused on some of the major challenges the digitalization process has to face, particularly privacy issues, system complexity and opacity, and ethical concerns related to legal aspects and healthcare disparities. Analyzing these open issues, we aim to present some of the future directions that in our opinion should be pursued to implement AI in clinical practice.