Humans have struggled against the negative impact of weeds since the cultivation of crops commenced around 10,000 b.c. Weed control technologies have evolved from hand-weeding to include primitive hoes, animal-powered implements, mechanically powered implements, biological control, and chemical control. Herbicides are often the most reliable and least expensive method of weed control available, and the success of herbicides is largely responsible for the abundant and sustained food production necessary to support an increasing world population. Pesticide resistance evolved in insects, fungi, and bacteria long before it was observed in weeds. Herbicide-resistant weeds were predicted shortly after the introduction of herbicides. Target-site resistance is the result of a modification of the herbicide-binding site, which precludes a herbicide from effectively binding.