Osteoclasts are large cells derived from the monocyte-macrophage hematopoietic cell lineage, whose primary function is to degrade bone in various physiological contexts. Reversible phosphorylation of tyrosine residues in proteins is known to play significant roles in regulating the function of osteoclasts, much as it does in other cell types. Protein tyrosine phosphatases (PTPs) are among the major regulators of this process, but significant gaps exist in our knowledge of which phosphatases function in osteoclasts and the nature of their precise cellular and molecular roles. We review here the roles of the four tyrosine phosphatases that are known currently to be expressed in osteoclasts--PTPRO, PTP epsilon (PTPepsilon), SHP-1, and PTP-PEST. Of these, PTPRO and PTPepsilon support osteoclast activity, whereas SHP-1 inhibits it. Much future research is required to uncover additional PTPs that function in osteoclasts and provide full molecular-level accounting of their respective roles in osteoclasts.