Large-scale CRISPR-Cas pooled screens have shown great promise to investigate functional links between genotype and phenotype at the genome-wide scale. In addition to technological advancement, there is a need to develop computational methods to analyze the large datasets obtained from high-throughput CRISPR screens. Many computational methods have been developed to identify reliable gene hits from various screens. In this review, we provide an overview of the technology development of CRISPR screening platforms, with a focus on recent advances in computational methods to identify and model gene effects using CRISPR screen datasets. We also discuss existing challenges and opportunities for future computational methods development.