The development of artificial intelligence (AI) and machine learning (ML)-based systems in medicine is growing, and these systems are being used for disease diagnosis, drug development, and treatment personalization. Some of these systems are designed to perform activities that demand human cognitive function. However, use of these systems in routine care by patients and caregivers lags behind expectations. This paper reviews several challenges that healthcare systems face and the obstacles of integrating digital systems into routine care. This paper focuses on integrating digital systems with human physicians. It describes second-generation AI systems designed to move closer to biology and reduce complexity, augmenting but not replacing physicians to improve patient outcomes. The constrained disorder principle (CDP) defines complex biological systems by their degree of regulated variability. This paper describes the CDP-based second-generation AI platform, which is the basis for the Digital Pill that is humanizing AI by moving closer to human biology via using the inherent variability of biological systems for improving outcomes. This system augments physicians, assisting them in decision-making to improve patients’ responses and adherence but not replacing healthcare providers. It restores the efficacy of chronic drugs and improves adherence while generating data-driven therapeutic regimens. While AI can substitute for many medical activities, it is unlikely to replace human physicians. Human doctors will continue serving patients with capabilities augmented by AI. The described co-piloting model better reflects biological pathways and provides assistance to physicians for better care.