DNA damage impairs cell growth by delaying or preventing critical processes such as DNA replication and chromosome segregation. In normal proliferating cells, initiation of these processes is controlled by genetically-defined pathways known as checkpoints. Tumors often acquire mutations that disable checkpoints and cancer cells can therefore progress unimpeded into S-phase, through G2 and into mitosis with chromosomal DNA damage. Checkpoint bypass in cancer cells is associated with cell death and loss of proliferative capacity and therefore is believed to contribute to the efficacy of DNA-damaging therapies. Are cancer cell clones that bypass checkpoints invariably more sensitive to DNA damage than checkpoint-proficient cells in normal tissues? We present evidence that the inherent survival of damaged human cells can be surprisingly independent of checkpoint control.