Transgenic crops producing insecticidal proteins from the bacterium Bacillus thuringiensis (Bt) control some important insect pests, including the pink bollworm (Pectinophora gossypiella) one of the world’s most damaging pests of cotton. However, the evolution of resistance by pests reduces the efficacy of Bt crops. Here, we review field outcomes with Bt cotton and pink bollworm during the past quarter century among the top three cotton producing countries: practical resistance in India, sustained susceptibility in China, and eradication of this invasive pest from the United States. We compare the molecular genetic basis of pink bollworm resistance between lab-selected strains from the U.S. and China and field-selected populations from India for two Bt proteins (Cry1Ac and Cry2Ab) produced in widely adopted Bt cotton. Both lab- and field-selected resistance are associated with mutations affecting the cadherin protein PgCad1 for Cry1Ac and the ATP-binding cassette transporter protein PgABCA2 for Cry2Ab. The results imply lab selection is useful for identifying genes important in field-evolved resistance to Bt crops, but not necessarily the specific mutations in those genes.