In an effort to define the major unanswered questions in bone cell biology and suggest new approaches to answering these questions, I have outlined the bone remodeling cycle and briefly described the major local and systemic factors that regulate bone cell function. These factors include calcium-regulating and systemic hormones as well as locally produced prostaglandins, cytokines, and growth factors. To understand the individual roles of this large number of regulators, it will be necessary to develop new approaches to measure their production and activity in bone under physiologic and pathologic conditions. Quantitative methods in molecular and cellular biology have been developed that should make this identification possible.