Seafood refers to several distinct groups of edible aquatic animals including fish, crustacean, and mollusc. The two invertebrate groups of crustacean and mollusc are, for culinary reasons, often combined as shellfish but belong to two very different phyla. The evolutionary and taxonomic diversity of the various consumed seafood species poses a challenge in the identification and characterisation of the major and minor allergens critical for reliable diagnostics and therapeutic treatments. Many allergenic proteins are very different between these groups; however, some pan-allergens, including parvalbumin, tropomyosin and arginine kinase, seem to induce immunological and clinical cross-reactivity. This extensive review details the advances in the bio-molecular characterisation of 20 allergenic proteins within the three distinct seafood groups; fish, crustacean and molluscs. Furthermore, the structural and biochemical properties of the major allergens are described to highlight the immunological and subsequent clinical cross-reactivities. A comprehensive list of purified and recombinant allergens is provided, and the applications of component-resolved diagnostics and current therapeutic developments are discussed.