Non-typeable Haemophilus influenzea (NTHi) is a human adapted pathogen, responsible for a significant disease burden in young children and the elderly. NTHi infections are a major driver of antibiotic use in children and antimicrobial resistance is an emerging problem. The first stage in NTHi pathogenesis is adherence to the host nasopharynx. Adherence requires intimate contact with specific host receptors by surface-located bacterial proteins called adhesins. In order to better understand host pathogen interactions for NTHi, a thorough characterisation of both the mode of regulation and the receptor(s) bound by these adhesins is required. This project will characterise a number of NTHi surface proteins: the unstudied protein NTHI1101, the autotransporters Lav and Hia, and the HMW1/2 adhesins. These proteins have been selected for investigation due to their location on the bacterial cell surface, and high conservation between strains where they are encoded. Our characterisation of NTHI1101 shows that this protein is required for host cell invasion, but not adherence. Our work on the autotransporter Lav shows that this protein is phase-variably expressed (it is switched ON and OFF at random) and is required for host cell adherence. Sequence analysis of Lav in multiple NTHi strains demonstrates three distinct variants present in NTHi, each encoding a different extra-cellular domain, resulting in binding to distinct host glycan receptors. Our analysis of Hia and HMW shows that these proteins bind host glycan structures located in the human airway, and that Hia is required for host cell adherence and biofilm formation. This work has determined that all four of these major NTHi surface proteins are required for key stages of pathogenesis. Future work will continue our detailed study of these adhesins in order to further understand their precise role in NTHi colonisation and disease.