Thaumatin-like proteins (TLPs) regard a highly complex protein family associated with host defense and developmental processes in plants, animals, and fungi. They exhibit high diversity in angiosperms, where they have been classified as the PR-5 (Pathogenesis-Related-5) protein family. In plants, TLPs exhibit a variety of properties associated with their structural diversity, being mostly associated with responses to biotic stress, besides some predicted activity under drought and osmotic stresses. The present review covers aspects related to the structure, evolution, gene expression, and biotechnological potential of TLPs. The efficiency of the discovery of new TLPs is below its potential considering the availability of omics data. Furthermore, we present an exemplary bioinformatics annotation procedure that was applied to cowpea (Vigna unguiculata) transcriptome, including libraries of two tissues (root and leave), two stress types (biotic/abiotic) and generated using different sequencing approaches. Even without using genomic sequences, the pipeline uncovered 56 TLP candidates in both tissues and stresses. Interestingly, abiotic stress (root dehydration) was associated with a higher number of modulated TLP isoforms. The nomenclature used so far for TLPs was also evaluated, considering TLP structure and possible functions identified to date. It is clear that plant TLPs are promising candidates for breeding purposes and for plant transformation aiming at a better performance under biotic and abiotic stresses. The development of new therapeutic drugs in the fight against human fungal pathogens also deserves attention. Despite that, applications derived from TLP molecules are still beyond their potential, as it is evident in our review.