: Dipeptidyl-peptidase-4 (DPP-4) is a surface bound ectopeptidase that is commonly known as CD26 or adenosine deaminase binding protein. DPP-4 is membrane anchored but it can be cleaved by numerous proteases including matrix-metalloproteinases (MMPs). DPP-4 is expressed by endothelial and epithelial cells, the kidney, intestine and cells of the immune system; it has a broad spectrum of biological functions in immune regulation, cancer biology and glucose metabolism.: This article sheds light on the functions of DPP-4, the molecular mechanisms that govern its expression, it’s role in the pathogenesis of common respiratory illnesses and potential as a therapeutic target.: DPP-4 has a deleterious role in respiratory disease. Its biological functions, key molecular pathways, interactions and associations are slowly being elucidated. Progressing our knowledge of the role of this multi-faceted molecule may yield vital and novel therapies for respiratory diseases such as lung cancer, asthma, and chronic obstructive pulmonary disease (COPD).