The PML and SP100-containing nuclear bodies (NBs) represent the best-studied example of a defined nuclear substructure the integrity of which is compromised in certain human diseases, including leukemia, neurodegenerative disorders and viral infection. Although recent progress has underscored the unexpectedly broad involvement of NB constituents in the control of cell growth, gene regulation and apoptosis in both pathological and normal contexts, evidence for a specific physiological activity within the NBs remains scant, thus precluding a unifying hypothesis for NB function.