Infectious diseases represent a major threat to human health. To develop urgently needed new control strategies, a transition from research focusing on individual factors to a more integrated system-level analysis might be needed. Such an approach faces great challenges and might require development of new concepts in large-scale data analysis. Here, I discuss for the well-characterized model pathogen Salmonella, how extensively studied metabolism can be used as a training field for infection biology at the systems level. Extensive experimental data can be analyzed in context using metabolic network visualization tools and in silico modeling based on genome-scale metabolic reconstructions. Suitable approaches to obtain still missing comprehensive quantitative data on Salmonella nutrition in infected host tissues are described. Such an integrated investigation of Salmonella metabolism during infection will enable an unprecedented large-scale understanding of pathogen in vivo activities, help to evaluate concepts and strategies for system-level analysis of host/pathogen interactions in general, and provide a basis for rational development of novel antimicrobials and efficacious live vaccines.