Increasingly it is being realized that despite considerable advancements in therapeutic interventions relatedto treatment of cancer, satisfactory results are still difficult to achieve. Rapidly accumulating evidence has startedto shed light on the fact that cancer cells escape from death via constitutive activation of pro-survival signalingcascades. Cell biology and genetics have extensively enhanced our current understanding of the molecularmechanisms that underlie loss of apoptosis in cancer cells. This review is focused on ionizing radiation mediatedrestoration of TRAIL mediated apoptosis as evidenced by cell culture and animal model studies. Moreover, wealso bring to the limelight radiation induced expression of miRNAs and how miRNAs further control responseof cancer cells to radiation.