Osteoclasts are the principal mediators of bone resorption. They form through the fusion of mononuclear precursor cells under the principal influence of the cytokines macrophage colony stimulating factor (M-CSF, aka CSF-1) and receptor activator of NF-κB ligand (RANKL, aka TNFSF11). Sexual dimorphism in the development of the skeleton and in the incidence of skeletal diseases is well described. In general, females, at any given age, have a lower bone mass than males. The reasons for the differences in the bone mass of the skeleton between women and men at various ages, and the incidence of certain metabolic bone diseases, are multitude, and include the actions of sex steroids, genetics, age, environment and behavior. All of these influence the rate that osteoclasts form, resorb and die, and frequently produce different effects in females and males. Hence, a variety of factors are responsible for the sexual dimorphism of the skeleton and the activity of osteoclasts in bone. This review will provide an overview of what is currently known about these factors and their effects on osteoclasts.