Glyphosate provides excellent weed control in the vast majority of times that it is applied. However, weeds are not controlled as expected in certain instances. Several factors may be responsible for these control failures. It is important to understand these factors so steps can be taken to avoid poor performance. There are three distinct places where glyphosate interacts with other elements when it is applied: 1) in the spray tank; 2) on the leaf surface; and 3) in the weed. This article reviews the potential for these interactions to reduce glyphosate performance.