Amid the aquaculture boom, chemical contaminants, diseases, and improper nutrition persist as threats to the sustainability of aquaculture. The accumulation of lipid droplets in different tissues has emerged as a hallmark in aquatic animals exposed to these stressors. While abundant knowledge is available on lipid droplets in mammals, relatively little is known in aquatic animals. Recently, interest in lipid droplets has grown in parallel with the recognition that they are actively engaged in the regulation of stress responses, metabolic modulation, infections, and immune response in different aquatic animals. This review first outlines the diversity of lipid droplets protein in various aquatic animals and discusses the function of lipid droplets in maintaining cellular homeostasis by contacting other organelles. Subsequently, the mechanisms of lipid droplet biogenesis in response to various chemical contaminants are summarized. Additionally, we describe the complex roles of lipid droplets in the host‐pathogen dynamic and the link between excessive lipid droplets accumulation and unwanted metabolic diseases in several aquatic animals. Finally, the potential application of lipid droplets in aquaculture is presented. A better understanding of the dynamics and functions of lipid droplets will facilitate the development of lipid droplets‐based therapeutic strategies, thereby improving the sustainability of aquaculture.