Casein kinase 2 (CK2), a highly conserved, multifunctional serine/threonine protein kinase, is critically important for the regulation of a plethora of processes in eukaryotes, such as cell proliferation, differentiation, and death. CK2 is expressed in all tissues; in particular, its amount and activity are elevated in tumor cells. Unlike many regulatory proteins, CK2 permanently adopts an active conformation. The anti-apoptotic functions of CK2 are of utmost importance. CK2 is capable of regulating cell survival at multiple levels, including DNA repair; the NF- B, Wnt, PI3K/Akt, and JAK-STAT signaling cascades; chaperones; activation of antiapoptotic proteins; and downregulation of pro-apoptotic counterparts, in particular, caspases. The versatility of CK2-mediated phosphorylation ensures the survival of tumor cells exposed to stimuli varying in origin and cytotoxicity mechanisms. Such manifold mode of CK2-dependent survival makes the enzyme an important target for antitumor therapy.