Generation of in vitro organoid models from pluripotent stem cell holds great promise for disease modeling, drug development, and tissue engineering. Cerebral organoids are complex three-dimensional (3D) structures that form by aggregation and self-organization of pluripotent cells, ultimately mimicking some aspects of the physiologically complex, multicellular, and layered architecture of the brain. However, significant variability and experimental challenges exist in organoid formation protocols. One such challenge is the large amount of cell death when pluripotent cells are dissociated and aggregated into 3D structures. Currently, the ROCK inhibitor Y-27632 is the most widely used reagent to improve cell survival. Nevertheless, poor cell survival and emergence of debris are evident even after treatment with Y-27632 suggesting that uncontrolled cell stress introduces an inherent systematic shortcoming in currently used protocols. Here, we used a novel small molecule cocktail, recently developed at NCATS, that greatly enhances cell survival during cerebral organoid formation. Improved cell survival at the onset of sphere formation generated larger, healthier and better controlled organoids. Ongoing molecular and functional experiments are aimed at demonstrating that optimal cell survival enhances morphogenesis, differentiation, and reproducibility of cerebral organoids.