The major types of posttranscriptional modification are the isomerization of uracil to pseudouridine, 2′-O-methylation of the ribose moieties and base methylation. In addition to their roles in pre-rRNA modification, both Dim1p and Cbf5p are required for pre-rRNA processing, and Pet56p is required for synthesis of mitochondrial large ribosomal subunits. This chapter discusses data on Dim1p and Cbf5p that provide insights on the type of systems that may act to coordinate the many steps in ribosome synthesis and the origins of the snoRNA-directed rRNA modification systems present in eukaryotic cells. Uncoupling of the dimethylation and prerRNA processing defects showed that Dimlp rather than the dimethylation activity is required for prerRNA processing. This observation did not, however, determine whether Dim1p is itself directly required for pre-rRNA processing. The binding of Dim1p to the pre-rRNA may therefore be monitored to ensure that it fulfills its functions in both modification and assembly. Ribosome synthesis is a highly dynamic process during which a vast number of processing, modification, and assembly reactions occur simultaneously. The requirement for Cbf5p in pre-rRNA processing appears to be quite different from the requirement for Dim1p. Eukaryotic ribosome synthesis involves very complex pre-rRNA processing and assembly pathways. These include numerous steps occurring in different cellular compartments and requiring a plethora of RNA and proteins, many of them in the form of snoRNPs that only transiently associate with the preribosomal particles. The archaea may hold the final clues to understanding the origins of the small nucleolar ribonucleoproteins (snoRNPs)-directed systems of rRNA modification.