Sex steroids are central to sexual development and reproduction, exerting pleiotropic effects on multiple tissues and organs throughout the lifespan of humans. Sex steroids are fundamental to skeletal development, bone homeostasis and immune function. The composite effect of sex-specific genetic architecture and circulating levels of sex-steroid hormones closely parallels differences in the immune response and may account for corresponding sex-related differences in risk for chronic periodontitis, with men exhibiting greater susceptibility than women. Age-associated reductions in sex steroids also provide insight into apparent temporal increases in susceptibility to periodontitis and alveolar bone loss, particularly among women. Chronic infection and inflammatory conditions, such as periodontal disease, provide a unique platform for exploring the interface of sex steroids, immunity and bone metabolism.