Throughout life, bone tissue is in a constant state of turnover. This process of bone remodeling is the result of a combination of sequential removal of bone tissue by osteoclasts and new bone deposition by osteoblasts. The osteopetroses are a heterogeneous group of skeletal disorders characterized by a generalized increase in bone mass caused by decreased bone resorption. Over the past decade, major contributions to our current knowledge on bone resorption have been made by studies of osteopetrotic mutations in animals. A considerable heterogeneity among the various osteopetrotic animals is observed, showing that a multiplicity of mutations may cause osteopetrosis. This review focuses on the spontaneous and experimentally induced osteopetrotic mutations in animals. We will discuss their impact on our current understanding of osteoclast biology and we will correlate, when possible, the animal models of osteopetroses to diseases in humans.