It has long been known that many bone diseases, including osteoporosis, involve abnormalities in osteoclastic bone resorption. As a result, there has been intense study of the mechanisms that regulate both the differentiation and bone resorbing function of osteoclast cells. Calcium (Ca(2+)) signaling appears to play a critical role in the differentiation and functions of osteoclasts. Cytoplasmic Ca(2+) oscillations occur during RANKL-mediated osteoclastogenesis. Ca(2+) oscillations provide a digital Ca(2+) signal that induces osteoclasts to up-regulate and autoamplify nuclear factor of activated T cells c1 (NFATc1), a Ca(2+)/calcineurin-dependent master regulator of osteoclastogenesis. Here we review previous studies on Ca(2+) signaling in osteoclasts as well as recent breakthroughs in understanding the basis of RANKL-induced Ca(2+) oscillations, and we discuss possible molecular players in this specialized Ca(2+) response that appears pivotal for normal bone function. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.