In this special issue of Current Topics in Medicinal Chemistry, the reader will find reviewed some of the hottest topics in the field of the non-reproductive effects of sex steroids. Cabrera-Muñoz et al., show that progesterone participates in the regulation of human brain tumors growth. The contribution of Martocchia suggests that sex steroid receptor modulating drugs provide new therapeutic approaches to autoimmune diseases. The role of sex steroid participation in the differentiation of stem cells to neurones is discussed by I. Velasco. Pérez-Torres and collaborators demonstrate that sex steroids play an important role in the appearance and development of renal diseases and the metabolic syndrome, the new epidemics of our century. Paris and Frye hypthetize that gestational stress, have effects on cognitive performance and/or neuronal integrity in the fetus, and that exposure to variable stress during gestation can perturb cognitive performance, concomitant with dendrite development in hippocampus and diencephalon. Muñoz-Cruz et al. thoroughly review the growing body of evidence that shows reciprocal relationship between sex steroids and the immune system, and conclude that understanding the mechanisms of action of sex steroids on immune cells is important for further progress in the development of novel therapies for chronic diseases associated to immune dysregulation. Besides, the effects of sexual steroids on pancreatic function and diabetes are reviewed by Morimoto et al. Yanes et al. review some of the contradictions raised in the context of the recently proposed critical period hypothesis, which takes into account the frame-time after cessation of ovarian function. Finally, another vey intetresting aspect of the non-reproductive effects of sex-steroids, is the related to some cognition-related aspects, which is reviewed by Picazo et al.