Invasive and endemic weeds pose recurring challenges for California land managers. The evolution of herbicide resistance in several species has imposed new challenges in some cropping systems, and these issues are being addressed by UC Cooperative Extension farm advisors, specialists and faculty. There are currently 24 unique herbicide-resistant weed biotypes in the state, dominated by grasses and sedges in flooded rice systems and, more recently, glyphosate-resistant broadleaf and grass weeds in tree and vine systems, roadsides and glyphosate-tolerant field crops. Weed scientists address these complex issues using approaches ranging from basic physiology and genetics research to applied research and extension efforts in grower fields throughout the state. Although solutions to herbicide resistance are not simple and are affected by many biological, economic, regulatory and social factors, California stakeholders need information, training and solutions to address new weed management problems as they arise. Coordinated efforts conducted under the Endemic and Invasive Pests and Disease Strategic Initiative directly address weed management challenges in California's agricultural industries.