The vast quantities of information generated by academic and industrial research groups are reflected in a rapidly growing body of scientific literature and exponentially expanding resources of formalized data including experimental data from “-omics” platforms, phenotype information, and clinical data. For bioinformatics, several challenges remain: to structure this information as biological networks enabling scientists to identify relevant information; to integrate this information as specific “knowledge bases”; and to formalize this knowledge across multiple scientific domains to facilitate hypothesis generation and validation and, thus, the generation of new knowledge. Risk management in drug discovery and clinical research is used as a typical example to illustrate this approach. In this chapter we will introduce techniques and concepts (such as ontologies, semantic objects, typed relationships, contexts, graphs, and information layers) that are used to represent complex biomedical networks. The BioXM™ Knowledge Management Environment is used as an example to demonstrate how a domain such as oncology is represented and how this representation is utilized for research.