Hydrapossesses remarkable regenerative capabilities which allow it to regrow lost or damaged body parts in a matter of days. Given that many key regulators of regeneration and development are evolutionarily conserved, Hydrais a valuable model system for studying the fundamental molecular mechanisms underlying these processes. In the past, kinase inhibitors have been useful tools for determining the role of conserved signaling pathways in Hydraregeneration and patterning. Here, we present a systematic screen of a commercially available panel of kinase inhibitors for their effects on Hydraregeneration. Isolated Hydragastric segments were exposed to 5 µM of each kinase inhibitor and regeneration of the head and foot regions were scored over a period of 96 hours. Of the 80 kinase inhibitors tested, 28 compounds resulted in abnormal regeneration. We directed our focus to the checkpoint kinase 1 (Chk1) inhibitor, SB 218078, considering the role of Chk1 in G2 checkpoint regulation and the importance of G2-paused cells in Hydraregeneration. We found that Hydraexposed to SB 218078 were unable to regenerate the head and maintain head-specific structures. Furthermore, SB 218078-treated Hydradisplayed a reduction in the relative proportion of epithelial cells; however, no differences were seen for interstitial stem cells or their derivatives. Lastly, exposure to SB 218078 appeared to have no impact on the level of mitosis or apoptosis. Overall, our study demonstrates the feasibility of kinase inhibitor screens for studying Hydraregeneration processes and highlights the possible role for HydraChk1 in head regeneration and maintenance.