Mycoplasmas are important production limiting pathogens in a number of domestic animals, but, although we have had complete genome sequences for the most important species for some time, our capacity to use these data to better understand the pathogenesis of the diseases these organisms cause has been limited because a large proportion of the predicted open reading frames appear to be unique to the mycoplasmas, or even to subsets of them. Therefore, a better understanding of the molecular pathogenesis of mycoplasmoses is likely to depend in part on elucidation of the function of these genes of unknown function. We have focussed on exploring the roles of proteins and lipoproteins that are predicted to be exposed to the external milieu on the cell surface, as they are most likely to be involved in direct interactions with the host. Using a combination of bioinformatic analyses and exploration of the biochemical functions of purified recombinant protein expressed from these genes of unknown function we have been able to attribute a range of roles to several of these cell surface proteins. In some cases individual proteins have a number of functions and can be predicted to play multiple roles in the pathogenesis of disease. These roles include a capacity to adhere to components of the extracellular matrix, and potentially to host cell surfaces, to degrade complex host molecules to simpler substrates, and to bind the products of these degradative reactions, presumably to assist in transport of nutrients into the mycoplasma cell. These functional findings complement genetic studies that are identifying genes required for colonisation and persistence in experimentally infected hosts.