The chapter starts with the description of the state-of-the-art and the literature review, while introducing the general context of the simulative and complexity science methodologies applied to the critical information infrastructure protection. While introducing the general context, the authors illustrate the methodologies and their applications. The major objective is to investigate the pros and cons to facilitate the choice between the mainstream lines of research in critical information infrastructure protection. Theoretical and practical issues are balanced in order to provide the reader with a wider understanding of the problems at hand and with the appropriate methodological tools to face them. This discussion on the state-of-the-art by no means can be considered exhaustive, depending on the personal views of the authors and on the room available, nevertheless it is meant to explain the trends and the relevant points in the field. It is also worth mentioning, moreover, that with respect to other CI (oil, gas, power grid, etc.), only a small number of CII modelling case studies are available. The reader should be aware that the intention of the authors is not to provide a deep, theoretical, or philosophical analysis of the issue under consideration, rather to help from a practical point of view. © 2013, IGI Global.