NetBox is a Java-based software tool for performing network analysis on human interaction networks. It is pre-loaded with a Human Interaction Network (HIN) derived from four literature curated data sources, including the Human Protein Reference Database (HPRD), Reactome, NCI-Nature Pathway Interaction (PID) Database, and the MSKCC Cancer Cell Map. It currently supports a command line interface for connecting genes into a network, identifying statistically significant “linker” genes, partitioning the network into modules, and executing two random background models. Results are then made available to the end user as an HTML web page and a series of network and attribute files, which can be loaded into Cytoscape for visualization and further analysis.