Novel, responsive liposomes are introduced, assembled from DNA-programmed lipids allowing sequence selective manipulation of nanoscale morphology. Short, single-stranded DNA sequences form polar head groups conjugated to hydrophobic tails. The morphology of the resulting lipid aggregates depends on sterics and electronics in the polar head groups and, therefore, is dependent on the DNA hybridization state. The programmability, specificity, and reversibility of the switchable system are demonstrated via dynamic light scattering, transmission electron microscopy, and fluorescence microscopy.