Abstract: Herbicides control undesired grasses and weeds while leaving the crop relatively unharmed. Herbicide antidotes (safeners) protect crops from herbicide damage without protecting weeds. Resistance to herbicides means the survival of a segment of the population following treatment with an herbicide dosage lethal to the normal population. Three mechanisms that account for herbicide resistance are: alterations in the target site, enhanced metabolism and compartmentation of the herbicide. Plants metabolize most herbicides through a series of intermediates ultimately to non toxic compounds. The basic detoxification reactions are oxidation, reduction, hydrolysis and conjugation. Major oxidative reactions are catalyzed by Cytochrome P450 monooxygenases (P450s) while the enzymatic conjugation with glutathione (GSH) catalyzed by glutathione S-transferases (GSTs) is the major detoxification pathway. Resistance occurs in plants as the result of random and infrequent mutations. Cross-resistance refers to resistance to an herbicide the plant has not been previously exposed to but that has a mode of action similar to the original herbicide. Multiple-resistance refers to resistance to more than one class of herbicides with very different modes of action. Most of uses of molecular biology are to find new herbicide targets and to generate herbicide-resistant crops by inserting exogenous resistance genes into the crops or by selecting natural mutations. Unlike the generation of transgenics, recurrent selection of a natural mutant will select for homozygous resistant individuals. Transgenics bear and express both the native and transgenic enzymes; they are functionally heterozygous and will remain so. Nevertheless, precautions must be considered for risk assessment. The main risk is claimed to be that of the biotechnologically-derived herbicide resistant crops becoming ‘volunteer’ weeds, or their introgressing traits into a wild relatives. The final decision on risk/benefit is ultimately a balance between science, economics, local benefits, local values, pressure groups and local politics.