The cell surface of Gram-positive pathogens represents a complex association of glycopolymers that control cell division, homeostasis, immune evasion, tissue invasion, and resistance to antimicrobials. These glycopolymers include the peptidoglycan cell wall, wall-teichoic acids, lipoteichoic acids, and capsular polysaccharide. Disruption of individual factors often results in pleiotropic effects, making it difficult to discern regulation and function. In this review we collate recent work describing these pleiotropic phenotypes, and propose that this is due to coordinated regulation of biosynthesis or modification of these cell surface components. A better understanding of the regulatory networks that control the relative prevalence of each factor on the cell surface or their modulated functions may help facilitate the identification of new targets for antimicrobial therapy.