Why some animals have the ability to regenerate complex structures (i.e. limbs), while others cannot, remains an important and open question. Our work focuses on how the immune system is able to contribute to the regenerative responses in salamanders which are able to regenerate entire limbs following amputation. Next generation sequencing has opened the doors to the study of new models systems as it does not depend on available resources (e.g. antibodies, transgenics) to study biological processes that the molecular level. We employ next generation sequencing techniques on salamander tissues and immune cells to understand how the immune system contributes to and facilitates regeneration in highly regenerative species. The knowledge gleaned from these studies will provide a framework for understanding how to harness the immune system to promote pro-regenerative outcomes in patients.