Advances in the understanding of the biological roles of the lysyl oxidase family of enzyme proteins in bone structure and function are reviewed. This family of proteins is well-known as catalyzing the final reaction required for cross-linking of collagens and elastin. Novel emerging roles for these proteins in the phenotypic development of progenitor cells and in angiogenesis are highlighted and which point to enzymatic and non-enzymatic roles for this family in bone development and homeostasis and in disease. The explosion of interest in the lysyl oxidase family in the cancer field highlights the need to have a better understanding of the functions of this protein family in normal and abnormal connective tissue homeostasis at fundamental molecular and cellular levels including in mineralized tissues.