Through live confocal fluorescent analysis of the rapid synchronous divisions of the Drosophila embryo, we produced a detailed temporal and morphological analysis of the effects of cell cycle inhibitors, including clinically used anti-cancer drugs on nuclear and cytoskeletal events. In addition to providing a wealth of new information on the cellular effects of these drugs, these studies indicate that two of these drugs result in an abbreviated interphase, suggesting that they compromise an S-phase checkpoint operating in the early embryo. In parallel with these studies, we analyzed the sensitivity of larva homozygous for mutations in the conserved Drosophila S-phase checkpoint genes, grp (chk1) and mei-41 (ATM). These mutations were especially sensitive to these same two topoisomerase inhibitors. This correlation suggests new strategies for killing checkpoint compromised cells.