Background/Aims: Alterations of cytosolic Ca<sup>2+</sup>-activity ([Ca<sup>2+</sup>]<sub>i</sub>) are decisive in the regulation of tumor cell proliferation, migration and survival. Transport processes participating in the regulation of [Ca<sup>2+</sup>]<sub>i</sub> include Ca<sup>2+</sup> extrusion through K<sup>+</sup>-independent (NCX) and/or K<sup>+</sup>-dependent (NCKX) Na<sup>+</sup>/Ca<sup>2+</sup>-exchangers. The present study thus explored whether medulloblastoma cells express Na<sup>+</sup>/Ca<sup>2+</sup>-exchangers, whether expression differs between therapy sensitive D283 and therapy resistant UW228-3 medulloblastoma cells, and whether Na<sup>+</sup>/Ca<sup>2+</sup>-exchangers participate in the regulation of cell survival. Methods: In therapy sensitive D283 and therapy resistant UW228-3 medulloblastoma cells transcript levels were estimated by RT-PCR, protein abundance by Western blotting, cytosolic Ca<sup>2+</sup>-activity ([Ca<sup>2+</sup>]<sub>i</sub>) from Fura-2-fluorescence, Na<sup>+</sup>/ Ca<sup>2+</sup>-exchanger activity from the increase of [Ca<sup>2+</sup>]<sub>i</sub> (Δ[Ca<sup>2+</sup>]<sub>i</sub>) and from whole cell current (I<sub>ca</sub>) following abrupt replacement of Na<sup>+</sup> containing (130 mM) and Ca<sup>2+</sup> free by Na<sup>+</sup> free and Ca<sup>2+</sup> containing (2 mM) extracellular perfusate as well as cell death from PI -staining and annexin-V binding in flow cytometry. Results: The transcript levels of NCX3, NCKX2, and NCKX5, protein abundance of NCX3, slope and peak of Δ[Ca<sup>2+</sup>]<sub>i</sub> as well as I<sub>ca</sub> were significantly lower in therapy sensitive D283 than in therapy resistant UW228-3 medulloblastoma cells. The Na<sup>+</sup>/Ca<sup>2+</sup>-exchanger inhibitor KB-R7943 (10 µM) significantly blunted Δ[Ca<sup>2+</sup>]<sub>i</sub>, and augmented the ionizing radiation-induced apoptosis but did not significantly modify clonogenicity of medulloblastoma cells. Apoptosis was further enhanced by NCX3 silencing. Conclusions: Na<sup>+</sup>/Ca<sup>2+</sup>-exchanger activity significantly counteracts apoptosis but does not significantly affect clonogenicity after radiation of medulloblastoma cells.