Biopharmaceuticals are complex molecules often manufactured from living systems and their specificity and novelty holds great promise for the treatment of chronic diseases for which there are currently no cures. The inhalation route of biopharmaceutical drug delivery is attractive because the large surface area of the lung, and close proximity of the alveolar and vascular systems, maximizes the potential for drug delivery to the lung and/or systemic circulation. In addition, costs of delivery to the patient are potentially much reduced, in comparison with parental administration, since inhalation is non-invasive and likely to promote patient compliance. However, in comparison with small molecule drug development, developing an inhaled biopharmaceutical that is effective and safe for human use is associated with many challenges. This review considers some general principles of drug delivery to lung and issues associated with the translation of proof of concept studies to toxicology safety studies (e.g. aerosol generation, species selection, exaggerated pharmacology, and immunogenicity). This review also presents a summary of nonclinical and clinical data from inhaled biopharmaceuticals which are either marketed for human use or in Phase II clinical trials (e.g. DNase, insulin, human growth hormone, vaccines, therapeutic plasmid DNA complexes).