Several receptors for nongenomically initiated actions of progesterone (P4) exist, namely membrane-associated P4 receptors (MAPRs), membrane progestin receptors (mPRs), receptors for neurosteroids GABAA receptor (GABAAR), NMDA receptor, sigma-1 and -2 receptors (S1R/S2R), the classical genomic P4 receptor (PGR), and α/β hydrolase domain-containing protein 2 (ABHD2). Two drugs related to this field have been approved: brexanolone (Zulresso™) for the treatment of postpartum depression, and ganaxolone (Ztalmy™) for the treatment of CDKL5 deficiency disorder. Both are derivatives of P4 and target the GABAAR. Several other indications are in clinical testing. CT1812 (Elayta™) is also being tested for the treatment of Alzheimer’s disease (AD) in Phase 2 clinical trials, targeting the P4 receptor membrane component 1 (PGRMC1)/S2R complex. In this Review, we highlight emerging knowledge on the mechanisms of nongenomically initiated actions of P4 and its derivatives. The progesterone (P4) receptor membrane component 1 (PGRMC1)/sigma-2 receptor (S2R) complex may be of clinical significance in the treatment of Alzheimer’s disease. It is targeted by a small molecule (Elayta™), which is being tested in clinical trials. Furthermore, PGRMC1 shows promising preclinical results in several other indications, including the diagnosis and treatment of cancer.Membrane progestin receptors have also been shown to be involved in a multitude of different physiological functions. Information on the critical residues required for P4 binding to the receptor is available, although a translational outcome is still lacking.In the field of neurosteroids, brexanolone (Zulresso™) and ganaxolone (Ztalmy™) have been approved for the treatment of postpartum depression and CDKL5 deficiency disorder, respectively. Several other indications are being tested clinically.α/β Hydrolase domain-containing protein 2 (ABHD2) has been identified as a new P4 receptor; in addition to its role in the activation of CatSper, it also appears to be involved in several other nongenomic P4 actions.