Objective: To review the pharmacology, pharmacokinetics, efficacy, safety, and clinical use of Technosphere insulin. Data Sources: A MEDLINE search (1966–March 2010) was conducted for English-language articles using the terms AFREZZA, AFRESA, Technosphere insulin, pulmonary insulin, and inhaled insulin. Abstracts from the American Diabetes Association and European Association for the Study of Diabetes annual meetings, presented in 2004, 2005, 2006, 2007, 2008, and 2009 were also searched for relevant data. Study Selection and Data Extraction: English-language articles pertinent to the pharmacology, pharmacokinetics, efficacy, and safety of Technosphere insulin were reviewed. Data Synthesis: Technosphere insulin is an inhaled insulin product with a pharmacokinetic profile suitable to meet prandial insulin needs in patients with diabetes. Technosphere insulin has demonstrated efficacy in terms of postprandial and overall glycemic control, with efficacy and safety outcomes maintained for up to 4 years in one study. The overall tolerability profile for Technosphere insulin in clinical trials published to date has demonstrated a relatively low risk of hypoglycemia and weight gain when compared with subcutaneous mealtime insulins. Clinical trials to date have demonstrated safety in terms of pulmonary function, and the absorption of Technosphere insulin is not significantly altered in patients with chronic obstructive pulmonary disease or in those who smoke. Conclusions: The Technosphere delivery system allows for the rapid absorption of Technosphere insulin via the lung, making this product a potential option for prandial insulin coverage in both type 1 and type 2 diabetes. The device to administer the insulin is well designed, small, and easy to use. Technosphere inhaled insulin may provide a useful treatment option for patients resistant to or fearful of initiating prandial insulin injections.