Systems biology takes an interdisciplinary approach to the systematic study of complex interactions in biological systems. This approach seeks to decipher the emergent behaviors of complex systems rather than focusing only on their constituent properties. As an increasing number of examples illustrate the value of systems biology approaches to understand the initiation, progression, and treatment of cancer, systems biologists from across Europe and the United States hope for changes in the way their field is currently perceived among cancer researchers. In a recent EU-US workshop, supported by the European Commission, the German Federal Ministry for Education and Research, and the National Cancer Institute of the NIH, the participants discussed the strengths, weaknesses, hurdles, and opportunities in cancer systems biology.Cancer Res; 70(1); 12-3. ©2010 AACR. Defining Cancer Systems BiologyAiming at understanding the dynamic interactions among components of a cell, among cells and their interaction with the environment, cancer systems biology is an approach by which biomedical questions are addressed through integrating experiments in iterative cycles with mathematical modeling, simulation, and theory. Modeling is not the final goal, but is a tool to increase understanding of the system, to develop more directed experiments, and finally to enable predictions. This definition of cancer systems biology matches closely the definition of the EraSysBio consortium of 16 European ministries, funding bodies, and project management agencies from 13 countries. 29The most popular definitions of systems biology refer to "dynamics," "mechanisms," "principles," and "behaviors." The complexity of biological systems and/or functions arises from the interaction of a myriad of nonlinear spatiotemporal phenomena and components. The fact that most cellular processes, such as cell-cycle control, cell differentiation, and apoptosis, are inherently dynamical highlights the need for integrating mathematical modeling into life science and clinical research. A systems biology approach can help identify and analyze the principles, laws, and mechanisms underlying the behavior of biological systems.The participants of the strategic workshop concluded that advancing biomedical applications through systems biology approaches requires the development of new theoretical methodologies, such as novel techniques for databased system identification, theoretical concepts for the design of experiments, good methods for hypothesis testing, theoretical frameworks to couple processes occurring at (and across) different spatial and temporal scales, and