The dynamic processes of cell growth and cell division remain under constant surveillance. As one of the primary 'gatekeepers' of the cell, p53 has a major role in sensing a variety of stressors to maintain cellular homeostasis. Growth is driven by new protein synthesis, a process that requires robust manufacture of ribosomes in the nucleolus. Ribosome biogenesis is a complex process comprising transcription, modification, and processing of ribosomal RNA, production of ribosomal proteins (RPs) and auxiliary factors, and coordinated assembly of ribonucleoprotein particles to produce mature ribosomes. As the major function of the nucleolus, ribosome biogenesis demands a considerable amount of resources and must be maintained in a coordinated manner to ensure fidelity of the process. Perturbations to many aspects of ribosome biogenesis are thought to contribute to 'nucleolar stress' and trigger a RP-Mdm2-p53 stress response pathway. In this review, we will clarify how disruption to three major components of ribosome biogenesis can trigger nucleolar stress and activate p53, thereby lending support to a RP-Mdm2-p53 ribosome biogenesis surveillance pathway.