This review will focus on human cell-based experimental models to study respiratory diseases, in particular models of the large airways relevant to asthma and chronic obstructive pulmonary disease. Such models have the advantage of incorporating cells that can be derived from disease-relevant tissue and so have retained important genetic and epigenetic features that contribute to the human disease. These models can be used for mechanistic studies, target identification and validation and toxicological testing. While many models have been developed to varying degrees of sophistication, the challenge remains to develop an integrated system that recapitulates the complex cell-cell and cell-matrix interactions that occur in vivo and to provide these with a 'circulation' to study the dynamics of immune and inflammatory cell influx and efflux.