The Lewis and Clark expedition in the early years of the nineteenth century is the most famous expedition in American history. Thomas Jefferson dispatched Lewis and Clark to negotiate with the Indians. There were two major missions behind Lewis and Clark's negotiations with the Indians: 1. to befriend the Indians to trade with the Americans; 2. to make peace among the Indian tribes. In the end, the missions failed. This article discusses the reasons for this failure by focusing on the major events in the Lewis and Clark expedition.