Biologically tolerant plasmas (BTPs) are plasmas with gas temperatures less than 40 °C that are generated near atmospheric pressures and in non-toxic gases such as air or helium. BTPs have recently garnered great interest as a therapeutic for cancer. Here, we review and discuss conventional cancer treatments, some of the plasma devices that are currently used and the influence of BTPs on cancer cells such as melanomas, carcinomas, and leukemia. The active agents of BTPs have been investigated and reveal the presence of reactive oxygen species (ROS) such as O, O2−, O3, and OH as well as reactive nitrogen species (RNS) such as NO and NO2. ROS and RNS exhibit oxidative properties and trigger signaling pathways in biological cells. In cancer cells, different doses and plasma induce signaling pathways including apoptosis.