The diverse fields of Omics research share a common logical structure combining a cataloging effort for a particular class of molecules or interactions, the underlying -ome, and a quantitative aspect attempting to record spatiotemporal patterns of concentration, expression, or variation. Consequently, these fields also share a common set of difficulties and limitations. In spite of the great success stories of Omics projects over the last decade, much remains to be understood not only at the technological, but also at the conceptual level. Here, we focus on the dark corners of Omics research, where the problems, limitations, conceptual difficulties, and lack of knowledge are hidden.