<p>Cytokinesis is the process that physically separates two sibling cells, ensuring the proper partitioning of the nuclear and cytoplasmic contents at the end of cell division. Cytokinesis requires a fine-tuned molecular machinery that has to be assembled with high spatiotemporal precision. Drosophila melanogaster is an ideal model system to investigate this cellular process. Genetic screens performed in spermatocytes, neuroblasts, and Schneider cells revealed numerous evolutionary conserved components. These genetically amenable systems have proven to be very useful to further elucidate the cellular and molecular mechanism of cytokinesis, significantly contributing to our current understanding of this important cellular process. As in other organisms, cytokinesis is largely dependent on the mitotic spindle, providing positional cues for cleavage furrow placement and progression. However, spindle-independent mechanisms could also be important during special cases of cytokinesis, such as asymmetric cell division. Thus, powerful fly genetics combined with single-cell analysis, live imaging, and biochemical assays will continue to provide important insights into the mechanism of cytokinesis.</p>