RNA interference (RNAi) is a molecular biological technique that has been extensively used to deplete specific components in cells and has been invaluable in determining the requirements of a given protein in a particular cellular process. One such system is the Drosophila S2 cell system, which is very sensitive to double-stranded RNA (dsRNA)–mediated gene silencing, but comprehensive study of the molecular components required for cellular processes in higher eukaryotes—such as mitosis and cell migration—has been more difficult to examine. Two papers from the University of California, San Francisco in the September 15 Journal of Cell Biology report comprehensive studies elucidating the molecular requirements for actin-binding proteins in lamella formation and motor proteins in mitosis.