The Lutheran Pastor Gotthilf Heinrich Ernst Muhlenberg (1753–1815) is remembered today as one of the pioneering figures in early American botany, which earned him the posthumous epithet "The American Linnaeus". This study traces Muhlenberg's contributions to American botany by reconstructing his vast transatlantic correspondence network over a period of more than 30 years. Working on the tenets of modern network studies and with information gathered from close to 700 original letters, diaries and publications, the present study places Muhlenberg both within his own web of correspondences and within the botanical discourse of his time. The result is a multi-faceted depiction of contemporary standards, codes and pitfalls of scientific communication in the so-called "Republic of Letters". As Muhlenberg's example shows, the very fabric of this Republic – open exchange of information – had a strong impact on the course and outcome of scientific research itself. This "Network Factor" becomes clearly visible in Muhlenberg's networking strategies, which he developed to protect his original work against the negative effects of the very medium he was working with.