Surface proteins are critical for the survival of gram-positive bacteria both in the environment and to establish an infection. Depending on the organism, their surface proteins are evolutionarily tailored to interact with specific ligands on their target surface, be it inanimate or animate. Most surface molecules on these organisms are covalently anchored to the peptidoglycan through an LPxTG motif found at the C-terminus. These surface molecules are generally modular with multiple binding or enzymatic domains designed for a specific survival function. For example, some molecules will bind serum proteins like fibronectin or fibrinogen in one domain and have a separate function in another domain. In addition, enzymes such as those responsible for the production of ATP may be generally found on some bacterial surfaces, but when or how they are used in the life of these bacteria is currently unknown. While surface proteins are required for pathogenicity but not viability, targeting the expression of these molecules on the bacterial surface would prevent infection but not death of the organism. Given that the number of different surface proteins could be in the range of two to three dozen, each with two or three separate functional domains (with hundreds to thousands of each protein on a given organism), exemplifies the complexity that exists on the bacterial surface. Because of their number, we could not adequately describe the characteristics of all surface proteins in this chapter. However, since the streptococcal M protein was one of the first gram-positive surface protein to be completely sequenced, and perhaps one of the best studied, we will use M protein as a model for surface proteins in general, pointing out differences with other surface molecules when necessary.