Waterhemp is a dioecious (male and female flowers on separate plants) pigweed with a high genetic diversity. Consequently, this pigweed has a high propensity to adapt to control tactics and has evolved resistance to herbicides from as many as 6 or 7 different herbicide groups (HGs). Out of 75 waterhemp populations collected from corn/soybean fields in Iowa in fall 2019, almost 25% had a four-way multiple resistance to HGs 2 (ALS inhibitors), 5 (atrazine), 9 (glyphosate), and 14 (PPO inhibitors). It is important to use a diverse herbicide program with multiple, effective sites of action to reduce overreliance on any single herbicide and slow further development of herbicide resistance in waterhemp.