Single-cell technologies have undergone a significant transformation, expanding from their initial focus on transcriptomics to encompass a diverse range of modalities. Recent advancements have markedly improved scalability and reduced costs, facilitating the processing of larger cell populations and broadening the scope of single-cell research. The incorporation of clustered regularly interspaced short palindromic repeats (CRISPR)-based perturbations has revolutionized the field by enabling precise functional genomics and detailed studies of gene regulation at the single-cell level. Despite these advancements, challenges persist, particularly in achieving genome-wide perturbations and managing the complexity of high-throughput data. This review discusses the technological milestones that have driven these changes, the current limitations of single-cell CRISPR technologies, and the future directions needed to address these challenges and advance our understanding of cellular biology. (c) 2024 The Author(s). Published by Elsevier Inc. on behalf of Korean Society for Molecular and Cellular Biology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).