There are several alternative herbicides with different modes of action for control of invasive plants in natural areas. Of the four classes of herbicides commonly used on invasive plants in natural areas of Florida, the acetolactate synthase (ALS) inhibitors, imazapyr, imazapic, and metsulfuron methyl, are the most likely to select for resistance. Invasive plants that have attributes such as numerous seed or spore production and log distance dispersal capabilities are most likely to develop resistance to herbicides following repeated application. In Florida, these species include Old World climbing fern (Lygodium microphyllum), cogongrass (Imperata cylindrica), torpedo grass (Panicum repens), and tropical soda apple (Solanum viarum). The best scenario for treatment of invasive plants in Florida's natural areas, to minimize potential for development of resistance, is to rotate herbicides with different modes of action or use tank mixtures of two or more herbicides with different modes of action.