The advent of nanotechnology has transformed several industrial and medical technologies. There has been an extensive use of engineered nanoparticle-based products in myriad aspects of daily human use. In recent years, extensive research on the toxicity and health risks of nanoparticle exposure has raised a concern over the unrestrained use of nano-based products and applications. The airway is one of the primary routes of nanoparticle exposure, and several studies highlight the debilitating effects of acute or chronic nanoparticle exposure. Some of the common outcomes of nanoparticle exposure on the pulmonary system include inflammation, oxidative stress, and DNA damage. Moreover, nanoparticles have been shown to exacerbate chronic lung diseases like asthma and COPD-emphysema. In 482contrast, nanotechnology has very useful applications in pulmonary nanomedicine as a therapeutic and diagnostic tool. One of the important therapeutic applications of nanoparticles in airway diseases is the targeted delivery of DNA, short interfering RNA, drugs, or peptides to hematopoietic progenitor cells and pulmonary epithelium to control chronic pathophysiology of obstructive (Chronic Obstructive Pulmonary Disease, COPD, and asthma) and conformational disorders (cystic fibrosis, CF). In addition, nanosystems have important applications in imaging technologies used to diagnose various pulmonary complications. However, it is critical that polymers and chemical reagents used for nanoparticle synthesis are nontoxic and biodegradable. Moreover, these nano-based systems need to be fine-tuned for providing sustained drug delivery to the selected cell type to overcome potential toxicity and side effects. We propose that strategies for designing safe nano-based technologies for therapeutic and diagnostic (theranostic) applications in the airway diseases are needed.