Crustaceans are among the most diverse and ancient arthropods, thriving across widespread habitats and playing a pivotal role in aquatic food production. Their significant contribution to global food security and economic development has positioned them as key resources in meeting the demands of a growing global population. However, challenges such as enhancing the production of economically valuable species and managing infections arising from high-density aquaculture remain critical. A major limitation is the inadequate understanding of host–pathogen interactions at cellular and molecular levels, highlighting the need for advanced tools like crustacean cell lines for disease diagnosis and management. Despite efforts spanning over a century, the successful establishment of crustacean cell lines remains elusive. This highlights the necessity for a comprehensive retrospective analysis of previous research to extract actionable insights. This chapter aims to consolidate the current status, advancements, and applications of crustacean cell culture, focusing on studies conducted between 2010 and 2025. By addressing key impediments and proposing a way forward, this review seeks to guide future research efforts, advancing the development of crustacean cell lines as indispensable tools for aquatic animal health management and aquaculture sustainability.