Polyphenols are a broad class of compounds. Some are ingested in substantial quantities from nutritional sources, more are produced by medicinal plants, and some of them are taken as drugs. It is becoming clear, that a single polyphenol is impacting several cellular pathways. Thus, a network approach is becoming feasible, describing the interaction of a single polyphenol with cellular networks. Here we have selected icariin to draw a prototypic network of icariin activities. Icariin appears to be a promising drug to treat major age-related diseases, like neurodegeneration, memory and depressive disorders, chronic inflammation, diabetes, and osteoporosis. It interacts with several relevant pathways, like PDE, TGF-ß, MAPK, PPAR, NOS, IGF, Sirtuin, and others. Such networks will be useful to future comparative studies of complex effects of polyphenols.