This paper provides an overview of the use of Prolog and its derivatives to sustain research and development in the fields of bioinformatics and computational biology. A number of applications in this domain have been enabled by the declarative nature of Prolog and the combinatorial nature of the underlying problems. The paper provides a summary of some relevant applications as well as potential directions that the Prolog community can continue to pursue in this important domain. The presentation is organized in two parts: “small,” which explores studies in biological components and systems, and “large,” that discusses the use of Prolog to handle biomedical knowledge and data. A concrete encoding example is presented and the effective implementation in Prolog of a widely used approximated search technique, large neighborhood search, is presented.