Many of the benefits of artificial intelligence (AI) are expected to emerge in the context of complex systems that become increasingly intelligent. The transformation of complex systems into complex intelligent systems (CoIS) create a new landscape, not only related to technology development but also to the management and decision-making processes connected to these systems. This chapter seeks to create a new understanding of decision-making with AI in the context of CoIS and outlines 3 central views of decisions making, including (1) the decision-maker, (2) the decision-making process and (3) the decision space. To illustrate several of the new and emerging prerequisites for CoIS, the emerging field of personalized medicine is used as an example disclosing several of the implication of AI integration in decision-making. By outlining the implications of these findings, the chapter contributes with a new understanding of dynamic of human- AI decision-making in the context of CoIS.