Research embracing systems biology approaches and careful analysis of the critical host response has greatly expanded our understanding of infectious diseases. First-generation studies based on genomics and proteomics have made significant progress in establishing the foundation for network-based investigations on virus-host interactions. More recently, data from complementary high-throughput technologies, such as siRNA and microRNA screens and next-generation sequencing, are augmenting systems level analyses and are providing a more detailed and insightful multidimensional view of virus-host networks. Together with advances in data integration, systems biology approaches now have the potential to provide profound impacts on translational research, leading to the more rapid development of new therapeutics and vaccines for infectious diseases. In this review, we highlight new high-throughput technologies, a new philosophy for studying virus-host interactions, and discuss the potential of systems biology to facilitate bench-to-bedside research and create novel strategies to combat disease. Can we save the world using these approaches? Read on.