A variety of different microbicides employing different mechanisms of action (MOA) are used to control microbial growth in cooling water systems. Although dosing strategies are often based on the target organisms and their behavior within the system, targets within the microbes can be equally important for designing and optimizing an effective treatment program. In addition, an understanding of the mechanisms of the microbicides can often provide insight into the proper use of the microbicides, and can be a useful tool in troubleshooting problems. Cooling water microbicides can be classified based on their mechanism of action. These classes are: oxidants, electrophiles, lytic compounds and protonophores. The mechanisms of action of different classes of cooling water microbicides will be presented, including implications of MOA on dosing strategies and the prevention of resistance and tolerance. Keywords: mechanism, biocide, isothiazolone, water treatment, bacteria