A field study was conducted over 2 yr to compare efficacy and economics of glyphosate-resistant, sulfonylurea-tolerant, and conventional soybean (Glycine max) weed control programs. Herbicide programs in the three soybean systems provided at least 90% control of browntop millet (Brachiaria ramosa), prickly sida (Sida spinosa), yellow nutsedge (Cyperus esculentus), pitted morningglory (Ipomoea lacunosa), and hemp sesbania (Sesbania exaltata) in most cases and postemergence (POST)-only programs were as effective as preemergence (PRE) followed by POST programs. Control of hyssop spurge (Euphorbia hyssopifolia) ranged from 93 to 100% in glyphosate-resistant soybean and from 88 to 100% in conventional soybean, but control was 60 to 100% in sulfonylurea-tolerant soybean. Sicklepod (Senna obtusifolia) control was at least 91% in glyphosate-resistant and sulfonylurea-tolerant soybean but was 81% for the standard SAN 582 plus imazaquin PRE and acifluorfen plus bentazon early POST treatment in conventional soybean. In glyphosate-resistant soybean, glyphosate applied sequentially resulted in an average yield of 3,020 kg/ha with a net return of $407/ha. In sulfonylurea-tolerant soybean, chlorimuron applied sequentially yielded 2,500 kg/ha with a net return of $271/ha. Conventional soybean yield with the standard herbicide program was 2,770 kg/ha with a net return of $317/ha. Yields for the cultivars were equivalent when the same standard herbicide program was used. When weed control is satisfactory and herbicide costs relatively comparable, yield potential of the cultivar and seed cost, including any technology fee, would be key factors in selecting a weed management system.