The production and processing of ribosomal RNA is a complex and well-coordinated nucleolar process for ribosome biogenesis. Progress in understanding nucleolar structure and function has lead to the unexpected discovery of the nucleolus as highly sensitive sensor of cellular stress and important regulator of the tumour suppressor p53. Inhibition of ribosomal RNA metabolism has been shown to activate a signalling pathway for p53 induction. This review elucidates the potential of classical and recently developed chemotherapeutic drugs to stabilise p53 by inhibiting nucleolar functions.