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The interplay of costs and ethics has increased the need for adequate models mimicking the human in vivo situation drastically. An adequate model has the ability to generate data which are predictive for a certain aspect of the human response, for example for the bioavailability.This review highlights how in vitro models can enrich pulmonary drug delivery research with more detailed insights in cellular and non-cellular barriers, allowing for faster improvements and significant innovations of inhalation drug products. Risk assessment in inhalation toxicology and aerosol medicines and related important guidelines (e.g. OECD, EMA) are mentioned as a fundament for the described methods. Principle decisions to find a suitable in vitro tool for the question being asked are discussed to support the individual selection. Depending on the cellular and non-cellular barrier, exemplary in vitro tools are described with their ability to reflect a certain part of the in vivo lung situation. The review closes with a short summary of more complex systems as well as their advantages and limitations.