Ribosome biogenesis is both necessary for cellular adaptation, growth, and proliferation as well as a major energetic and biosynthetic demand upon cells. For these reasons, ribosome biogenesis requires precise regulation to balance supply and demand. The complexity of ribosome biogenesis gives rise to many steps and opportunities where regulation could take place. For trans-acting factors involved in ribosome biogenesis in the nucleolus, there may be a dynamic coordination, both spatially and temporally, that regulates their functions from the transcription of rDNA to the assembly and export of preribosomal particles. Here we summarize most of the described regulations on ribosome biogenesis in the nucleolus. However, these may represent only a small fraction of a larger picture. Further studies are required to determine the initial signals, signal transduction pathways utilized, and the specific targets of these regulatory modifications and how these are used to control ribosome biogenesis as a whole.