In more than one decade, genomic research produced a huge amount of experimental data. Although these data are usually freely available on theWorld WideWeb, accessing them in a consistent and fruitful way is not always an easy task. One of the main causes of this problem can be recognized in the lack of user interfaces that are sufficiently flexible and, at the same time, highly interactive and cooperative and also semantically precise. This paper tackles this issues by presenting a semantics drive paradigm for formulating queries to genomic and protein databases. The paradigm is founded on knowledge-based reasoning capabilities, in order to provide the user with a semantics driven guide in the difficult task of building the intended query.