Reprogramming of a differentiated cell into a cell capable of giving rise to many different cell types, a pluripotent cell, which in turn could repopulate or repair nonfunctional or damaged tissue, would present beneficial applications in regenerative medicine. It was shown by different groups that germ cells can be reprogrammed to pluripotent stem cells in all diploid stages of development. Specification of germline lineage is one of the most essential events in development, since this process ensures the acquisition, modification, and reservation of the totipotent genome for subsequent generations. We and other groups have shown that adult male germline stem cells, spermatogonial stem cells, can be converted into embryonic stem cell-like cells that can differentiate into the somatic stem cells of three germ layers. Importantly, cultured germ cells demonstrate normal and stable karyotypes as well as normal patterns of genomic imprinting. Transplantation studies have begun in a variety of models in hopes of defining their potential application of pluripotent stem cells derived from germ cells to treat a wide variety of human conditions, including cardiovascular and neurological disorders. This chapter describes general considerations regarding molecular and cellular aspects of reprogramming of germ cells at different developmental stages to stem cells compared with their counterpart, embryonic stem cells.