The molecular pathways that govern human disease consist of molecular circuits that coalesce into complex, overlapping networks. These network pathways are presumably regulated in a coordinated fashion, but such regulation has been difficult to decipher using only reductionistic principles. The emerging paradigm of "network medicine" proposes to utilize insights garnered from network topology (eg, the static position of molecules in relation to their neighbors) as well as network dynamics (eg,

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... he unique flux of information through the network) to understand better the pathogenic behavior of complex molecular interconnections that traditional methods fail to recognize. As methodologies evolve, network medicine has the potential to capture the molecular complexity of human disease while offering computational methods to discern how such complexity controls disease manifestations, prognosis, and therapy. This review introduces the fundamental concepts of network medicine and explores the feasibility and potential impact of network-based methods for predicting individual manifestations of human disease and designing rational therapies. Wherever possible, we emphasize the application of these principles to cardiovascular disease. (Circ Res. 2012;111:359-374.) Non-standard Abbreviations and Acronyms CALM1 calmodulin CETP cholesterol ester transfer protein ChIP-ChIP chromatin immunoprecipitation followed by microarray analysis ChIP-Seq ChIP followed by sequencing FDA-AERS Adverse Events Reporting System of the FDA FDA Food and Drug Administration GWAS genome-wide association studies HCMV human cytomegalovirus LCMS likelihood-based causality model selection test LQTS long-QT syndrome MCA metabolic control analysis mRNA messenger RNA miRNA microRNA ODEs ordinary differential equations PPAR peroxisome proliferator-activated receptor PPI protein-protein interactions QTL quantitative trait loci 360 Circulation Research