Since the appearance of the first therapeutic active peptides and proteins produced by genetic engineering, there has been an ever-increasing demand to be able to deliver these drugs by routes other than the parenteral. For most drugs the need for alternative delivery systems is due to short-half lives in the bloodstream, large extents of first pass metabolism, or the possibility of obtaining endogenous-like plasma profiles. A wide variety of drugs have now been tested for bioavailability after respiratory, especially intranasal, administration. A small range of drugs (such as propranolol and progesterone) appears to be absorbed effectively via the nasal route and shows bioavailabilities comparable to the intravenous route. However, most drugs shows a much lower degree of absorption. The present review discusses the critical steps that have to be considered when attempting to deliver drugs effectively via the nasal and pulmonary routes and how it is possible by suitable formulation of delivery systems to overcome some of the most important barriers to drug absorption. Furthermore, the immunological responses to respiratory absorption of exogenous peptides and proteins and the potential for development of locally administered vaccines are reviewed.