Weeds impact proper crop growth and incur in significant yield losses if managed improperly. Soybeans growers worldwide rely heavily on herbicides for proper weed management, as these often offer selective, inexpensive control of troublesome weeds. However, it is well established and known that the repeated use of herbicides within a single mode of action coupled with the lack of use of other weed management tools can result in the selection of herbicide-resistant weed populations, a troublesome worldwide phenomenon which threatens food production sustainability. Here, key concepts regarding the evolution of weed resistance to herbicides are discussed, such as its development and types of mechanisms, as well as lessons learned from troublesome cases. The current reality of few new herbicide discoveries has added emphasis to herbicide-tolerant crop cultivars. History and development of genetically engineered, transgenic soybean is presented, starting from the release of RoundupReady® soybeans in the 90s, which revolutionized weed management in row crops, all the way to more recent technologies, such as dicamba and 2,4-D-tolerant traits.