It has long been known that the female sex is associated with a better clinical outcome in chronic renal diseases. Although many experimental, clinical, and epidemiological studies in adults have attempted to explain the difference in disease progression between females and males, a definitive understanding of the underlying mechanisms is still lacking. Hormone-modulating therapies are being increasingly used for various indications (such as post-menopausal hormone replacement, estrogen- or androgen-receptor antagonists for cancer therapy). Therefore, a deeper knowledge of the interaction between sexual hormones and progression of kidney disease is important, as hormone-modulating therapy for non-renal indication may influence both kidney structure and function. In addition, specific modulation of the sexual hormone system, such as the use of selective estrogen receptor modulators, may represent a therapeutic option for patients with renal diseases. Although conclusive data on this topic in the pediatric population are still lacking, the aim of this review is to familiarize pediatric nephrologists with gender-specific differences in renal physiology, pathophysiology, and the progression of kidney diseases. Experimental models that analyze the effects of sexual hormones on renal structure and function are discussed. It is hoped that this review will stimulate researchers to focus on pediatric studies that will provide a deeper insight into the interaction of gender hormones and the kidney both before and during puberty.