OVERVIEWWeeds present a continual challenge for profitable alfalfa production. The Roundup Ready (RR) production system, using transgenic alfalfa, has the potential to simplify weed management by improving broad-spectrum control of both annual and difficultto-control perennial weeds. The use of glyphosate, in combination with transgenic crops, has proven to be a reliable weed control strategy.However, weed species shifts and the selection for glyphosate-resistant weeds can result from the increased use of this technology if the crop is not managed properly from the outset. Aspects of the alfalfa production system both favor and discourage the occurrence of weed shifts and the evolution of resistant weeds. Alfalfa is a competitive perennial crop that is cut multiple times per year, making it difficult for most weeds to become established. On the other hand, the RR alfalfa system may be vulnerable to weed shifts and resistant weeds for several reasons: tillage typically only occurs between crops, alfalfa is produced over a wide geographical area and in large fields with a great diversity of weeds, and there is potential for long-term repeated use of a single herbicide because it is a perennial crop. In this publication we recommend an integrated weed management system designed to prevent the proliferation of tolerant or resistant weeds. Elements include crop rotation, rotations with herbicides of different modes of action (preferably soil-residual herbicides), tank mixtures, and irrigation and harvest timing. Successful adaptation of these concepts into production systems would assure the long-term effectiveness and sustainability of the Roundup Ready system in alfalfa. A preemptive approach is warranted; these strategies should be employed before weed shifts and weed resistance occur.