Fish mucus layers are the main surface of exchange between fish and the environment, and they possess important biological and ecological functions. Fish mucus research is increasing rapidly, along with the development of high-throughput techniques, which allow the simultaneous study of numerous genes and molecules, enabling a deeper understanding of the fish mucus composition and its functions. Fish mucus plays a major role against fish infections, and research has mostly focused on the study of fish mucus bioactive molecules (e.g., antimicrobial peptides and immune-related molecules) and associated microbiota due to their potential in aquaculture and human medicine. However, external fish mucus surfaces also play important roles in social relationships between conspecifics (fish shoaling, spawning synchronisation, suitable habitat finding, or alarm signals) and in interspecific interactions such as prey-predator relationships, parasite–host interactions, and symbiosis. This article reviews the biological and ecological roles of external (gills and skin) fish mucus, discussing its importance in fish protection against pathogens and in intra and interspecific interactions. We also discuss the advances that “omics” sciences are bringing into the fish mucus research and their importance in studying the fish mucus composition and functions.