Understanding the cellular mechanisms of platelet activation and their pharmacologic modulation is of major interest for basic and clinical research. Here we introduce a comprehensive human platelet repository (PlateletWeb) for systems biologic analysis of platelets in the functional context of integrated networks. Functional, drug, and pathway associations provide a first systemic insight into various aspects of platelet functionality and pharmacologic regulation. Detailed manual curation of recent platelet proteome and transcriptome studies yielded more than 5000 platelet proteins. Integration of protein-protein interactions with kinase-substrate relationships unraveled the platelet signaling network involving more than 70% of all platelet proteins. Analysis of the platelet kinome in the context of the kinase phylogenetic background revealed an over-representation of tyrosine kinase substrates. The extraction and graphical visualization of specific subnetworks allow identification of all major signaling modules involved in activation and inhibition. An in-depth analysis of DOK1 signaling identifies putative signal modulators of the integrin network. Through integration of various information sources and high curation standards, the PlateletWeb knowledge base offers the systems biologic background for the investigation of signal transduction in human platelets (http://plateletweb.bioapps.biozentrum.uni-wuerzburg.de).