Brazil is a large producer and exporter of crops in global terms. Weeds may be responsible for ~14% of crop losses, depending on the crop system. Herbicides occupy 58% of the Brazilian pesticide market; however, the continuous use of these products and the high selection pressure have led to the emergence of weeds resistant to herbicides. Today, there are 51 weed species reported as being resistant to herbicides in Brazil, of which 17 involves cross and multiple-resistance. Acetolactate synthase (ALS), acetyl coenzyme A carboxylase (ACCase) and 5-enolpiruvylshikimate-3-phosphate synthase (EPSPs) inhibitors are the herbicidal groups with the most resistance cases. Soybean, corn, rice, wheat and cotton present 30, 12, 10, 9 and 8 cases, respectively, occurring mainly in herbicide-resistant crop fields from the Southern and Central West regions of the country. To better understand the dimensions of herbicide resistance, in this chapter, we will explore the size of agricultural activity in Brazil, the pesticide market and the use of herbicides in the main crops. In addition, the agronomic, scientific-technical and economic aspects that have contributed, directly or indirectly, to the selection of resistant weeds will be discussed in order to have an overview of the economic impact of herbicide resistance management.