Intense research effort in low-temperature (or cold) atmospheric plasma application in bioengineering led to the foundation of a new field—plasma medicine. Cold atmospheric plasmas have the ability to perform minimally-invasive surgery that allows specific cell removal without influencing the whole tissue. The efficacy of cold plasma in a pre-clinical model of various cancer types (lung, bladder, breast, head, neck, brain, and skin) has been demonstrated. Both in vitro and in vivo studies revealed that cold plasmas selectively kill cancer cells. It was shown that: 1) cold plasma application selectively eradicates cancer cells in vitro without damaging normal cells; and 2) significantly reduces tumor size in vivo. Cold plasma treatment led to tumor ablation without affecting neighboring tumors. The two best known cold plasma effects, plasma-induced apoptosis and the decrease of cell migration velocity can have important implications in cancer treatment by localizing the affected area of the tissue and by decreasing metastasic development. In addition, cold plasma treatment has affected the cell cycle of cancer cells. In particular, cold plasma induces a twofold increase in cells at the G2/M-checkpoint in both papilloma and carcinoma cells at ∼24 hours after treatment, while normal epithelial cells did not show significant differences. It was shown that reactive oxygen species metabolism and oxidative stress responsive genes are deregulated.