The engineering of genes encoding insecticidal proteins from the soil bacterium Bacillus thuringiensis into crop plants offers numerous potential benefits to agriculture. Such crops could dramatically reduce the use of conventional broad-spectrum insecticides against insect pests, as well as remove the dependence of pest control on extrinsic factors including climate and the efficiency of traditional application methods. However, this area of biotechnology also introduces risks, especially that of pests adapting rapidly to resist genetically engineered toxins. To date, there are no substantiated reports of resistance selected directly by exposure to commercial genetically modified crops. However, resistance to conventional Bt sprays (selected in either the laboratory or the field) has now been reported in more than a dozen species of insect. Research into the causes and inheritance of such resistance mechanisms has provided valuable insight into the threats facing Bt plants, and into the likely efficacy of possible countermeasures. Tactics proposed for sustaining the effectiveness of Bt plants have many parallels with ones considered for managing resistance to conventional insecticides, but are more limited in scope due to the long persistence and constitutive expression of engineered toxins and the limited diversity of transgenes currently available. Indeed, for existing “single-gene” plants the only prudent and readily implementable tactic is to ensure that substantial numbers of pests survive in non-transgenic “refuges”, composed either of the crop itself or of alternative host plants. In the longer-term, stacking (pyramiding) of two or more genes in the same cultivar, or possibly rotations of cultivars expressing different single toxins, are potentially more durable options for resistance management. Whatever options are adopted, however, it is essential that Bt plants (and their successors) are exploited as components of multi-tactic strategies rather than as a panacea for all existing pest management problems. In reality, some localized difficulties with Bt plants due to resistance are probably inevitable, particularly in developing countries where quality control and resistance countermeasures may prove difficult to implement. Instead of signaling the failure of this area of biotechnology, such instances should be exploited as opportunities to analyze the underlying causes, and to strengthen the resolve for deploying insect-tolerant transgenic plants on a sustainable and global basis in order to realize their considerable potential contribution to world agriculture.