Bcl-2, Bcl-x(L), Mcl-1, and A1 are the predominant anti-apoptotic members of the Bcl-2 family in somatic cells. Malignant B lymphocytes are critically dependent on Bcl-2 or Bcl-x(L) for survival. In contrast, a new study by Glaser and colleagues in the January 15, 2012, issue of Genes & Development (pp. 120-125) demonstrates that Mcl-1 is essential for development and survival of acute myelogenous leukemia cells. These results provide new impetus for the generation of selective Mcl-1 inhibitors.