It is now increasingly accepted that many existing biological and medical ontologies can be improved by adopting tools and methods that bring a greater degree of logical and ontological rigor. In this chapter we will focus on the merits of a logically sound approach to ontologies from a methodological point of view. As we shall see, one crucial feature of a logically sound approach is that we have clear and functional definitions of the relational expressions such as ‘is_a’ and ‘part_of’. While this chapter is mainly concerned with the general issues of methodology, chapter 15, on ‘Spatial Representation and Reasoning’, will apply the methodology to the specific case of spatial relations. Although both chapters are self-contained, we recommend that they be seen as forming a unity.