The pituitary gland, often called the "master gland", orchestrates multiple effector hormonal organs and other glands by secreting various tropic hormones, which play a significant role in a myriad of physiological processes including skeletal modeling and remodeling, fat and glucose metabolism, and cognitive and psychological processes. The findings of the expression of receptors for each pituitary hormone and the hormone itself in skeleton, fat and immune cells suggested that their role is much broader than the traditional or classic role. Follicle-stimulating hormone (FSH), once believed to regulate gonadal function - gonadal development and maturation at puberty and gamete production during the fertile phase - is also found to involve in fat and bone metabolism as well as cognition, which provides us a better understanding of complex physiology. This emerging understanding of the non-reproductive role of FSH opens potential therapeutic opportunity to address detrimental health burden during and after menopause, namely osteoporosis, obesity and dementia. In this Review, we outline the current understanding of crosstalk between the pituitary, bone, adipose tissue and brain through FSH. The pre-clinical evidence from genetic and pharmacologic intervention in rodent models, and human data from population-based observation, genetic studies, and a small number of studies with interventional nature support an independent skeletal, lipogenic and cognitive effect of FSH and more.