As discussed in Chapter 1, herbicide resistance has been reported to most herbicide chemical classes and has been documented in 147 different weed species. 1 A complete and updated list can be found at http://www.weedscience.com. Resistance occurs as a result of heritable changes to biochemical processes that enable plant survival when treated with a herbicide. This chapter deals with the specific changes to plant biochemistry that endow resistance to herbicides. Any biochemical change that allows a plant to survive herbicide application can be selected. This means that even for the same herbicide, resistance can be endowed by a number of different biochemical mechanisms. Resistance can result from changes to the herbicide target site such that binding of the herbicide is reduced, or over-expression of the target site may occur. Alternatively, there may be a reduction in the amount of herbicide that reaches the target enzyme through detoxification, sequestration, or reduced absorption of herbicide. Finally, the plant may survive through the ability to protect plant metabolism from toxic compounds produced as a consequence of herbicide action. This chapter considers major mechanisms of resistance to herbicides in weed species where resistance has evolved in the field.