A critical goal of translational research is to convert basic science to clinically relevant actions related to disease prevention, diagnosis, and eventually enable physicians to identify and evaluate treatment strategies. Integrated initiatives are identified as valuable in uncovering the mechanism underpinning the progression of human diseases. Tremendous opportunities have emerged in the context of systems biology that aims at the deconvolution of complex phenomena to their constituent elements and the quantification of the dynamic interactions between these components through the development of appropriate computational and mathematical models. In this review, we discuss the potential role systems-based translation research can have in the quest to better understand and modulate the inflammatory response.