Viable horseradish roots of various sizes remain in the soil after harvest and can develop into volunteer plants in subsequent crops. Experiments were conducted to evaluate POST herbicides on volunteer horseradish control and to determine if efficacy is dependent upon horseradish root segment size, herbicide rate, horseradish cultivar, or horseradish shoot size at application. In the greenhouse, horseradish root segment size did not affect herbicide efficacy. Chlorimuron, cloransulam, imazamox, (2,4-dichlorophenoxy)acetic acid (2,4-D) amine, halosulfuron, and imazethapyr plus imazapyr provided greater than 95% foliar control of volunteer horseradish. Chlorimuron, halosulfuron, and 2,4-D amine were also among the herbicides that provided the greatest reduction in horseradish root biomass (69% or greater). Glyphosate provided little foliar control (76%) and root biomass reduction (57%) after one application. The efficacy of 2,4-D amine on horseradish foliage and root biomass increased with increasing herbicide rate; however, the response of horseradish to halosulfuron was similar for all rates evaluated. Root biomass reduction of the horseradish cultivar ‘1573’ was less responsive to 2,4-D amine and halosulfuron applications compared with ‘1038’ and ‘1722’. However, foliar injury from 2,4-D amine and halosulfuron was less for the horseradish cultivar ‘1038’ compared with ‘1573’ and ‘1722’. In field studies, 2,4-D amine applied to 15- and 30-cm-tall horseradish and halosulfuron applied to 15-cm-tall horseradish resulted in the greatest foliar and root biomass reduction. This study indicated that in-season control of volunteer horseradish in rotational crops may be achieved through proper herbicide selection.