Herbicide resistance in weeds is perhaps the most prominent research area within the discipline of weed science today. Incidence, management challenges, and the cost of multiple-resistant weed populations are continually increasing worldwide. Crop cultivars with multiple herbicide-resistance traits are being rapidly adopted by growers and land managers to keep ahead of the weed resistance tsunami. This Special Issue of Plants comprises papers that describe the current status and future outlook of herbicide resistance research and development in weedy and domestic plants, with topics covering the full spectrum from resistance mechanisms to resistance management. The unifying framework for this Special issue, is the challenge initially posed to all of the contributors: what are the (potential) implications for herbicide resistance management?