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Non-thermal application of physical plasma is rapidly gaining importance for the future therapy and prevention of chronic inflammatory diseases and tumors. Here, we outline the importance of this innovative and less invasive therapy option, particulary for the treatment and prevention of gynecological cancers. Atmospheric physical plasma at body temperature (cold physical plasma: CAP) is a highly reactive physical state. It is essentially different from the three known aggregate states and, therefore, usually called the fourth state of matter [1]. Due to its composition containing diverse reactive oxygen and nitrogen species (ROS, RNS), CAP is highly interactive with biological systems [2]. In 2004, Eva Stoffes' group (Eindhoven, The Netherlands) demonstrated for the first time CAP's impact on living tumor cell models [3,4,5,6]. From 2005 until today, the number of studies and original articles concerning CAP in oncology has increased exponentially as shown by a systematic review of Dubuc et al. [7]. A significant decrease of cell viability pointed to CAP as a promising treatment option in cancer therapy. Subsequent examinations showed that distinct cellular responses occur 24 h after CAP exposition. Beyond others, CAP treatment induced a shift in cell morphology and membrane architecture and led to the apoptotic fragmentation of genomic DNA [8]. Thus, CAP efficacy activates apoptotic cascades in tumor cells which is essential in cancer therapy. In contrast to cytotoxicity and subsequent induction of necrosis as seen within classical chemotherapy, the induction of apoptosis shows significantly reduced side effects on adjacent tissue. Perhaps most importantly, CAP treatment of malignant tissue results in the inactivation of cancer cells without severe inflammation, pain and swelling of the adjacent tissue [9]. Mutagenic effects of CAP treatment have been excluded by various experimental approaches [10,11,12]. CAP's specificity of selectively targeting malignant cells without primarily affecting non-malignant tissue has been extensively discussed; however, current data cannot prove this sufficiently. Especially in gyneco-oncology the focus of CAP-related research has increasingly shifted towards its potential clinical use against intraepithelial neoplasia and invasive cancer tissue. In several in vitro studies the effectiveness against gynecological cancer cells could already be proven [13,14,15,16,17,18,19,20]. Particularly breast cancer, ovarian cancer and cervical cancer will increasingly move to focus for direct and indirect (e.g. plasma-activated solutions) plasma treatment (Fig. 1).