The interactions with microRNAs (miRNAs) and their targets in plants is assumed to be dependent largely on complementarity between the two RNAs. Zheng et al. investigated the interactions between miR159 and its putative targets, mRNA of several MYB genes, each with similar complementarity to the miRNA. Genetic data however suggest that miR159 silences some of these MYB genes more effectively than others. The authors found that the presence of two stem-loop RNA structures adjacent to the miRNA target site enhanced the efficacy of miR159. The authors suggest that the function of the stem-loop structures might be to increase the likelihood of the target site being single-stranded, or might facilitate interactions with proteins that would affect silencing efficacy. These results show that sequence complementarity alone is not sufficient to determine the efficacy of miRNAs, but that flanking sequences and structures are also important. Plant Physiol.