Cumulative work on glucocorticoid (GC) regulation of genes in lymphoid cell cultures has revealed that apoptotic sensitivity to GCs depends on sufficient active GC receptors in the cells. The actions of the ligand-driven GC receptor that lead to apoptosis depend on interactions with other major cell-signaling systems, including the MAPK pathways, the cAMP/PKA pathway, the hedgehog pathway, the mTOR system and the c-myc system. The balance between these systems determines whether a given cell responds to GCs by undergoing apoptosis. A central core of networked genes may be found under GC control in many types of malignant, GC-sensitive cells. The partial core list identified should be tested in clinical cell samples from hematologic malignancies.