Progesterone (P4) is defined as a steroid female hormone that exerts a wide variety of biologic effects in the human organism. One of the key roles of P4 is in the female reproductive system, pregnancy and mammary development. However, it also acts in many other organs, including cardiovascular and central nervous systems. The wide range of biologic effects of this steroid hormone is associated with the presence of several progesterone receptor isoforms, both in the nucleus and in the cytoplasm, as well as the huge number of molecular mechanisms, namely target gene transcription or phosphorylation cascade signaling pathways, evoked by their stimulation. In addition, synthetic progestins are widely used among the female gender, either as contraceptive agents or hormone replacement therapy. Since P4 has been linked to several pathological stages, including several types of cancer, care must be taken regarding the general employment of this hormone. Herein, we review the role of progesterone and their target signaling pathways in physiological and pathological conditions.