The collagen domain, which is defined by the presence of the Gly-X-Y triplet repeats, is amongst the most versatile and widespread known structures found in proteins from organisms representing all three domains of life. The streptococcal collagen-like (Scl) proteins are widely present in pathogenic streptococci, including Streptococcus pyogenes, S. agalactiae, S. pneumoniae, and S. equi. Experiments and bioinformatic analyses support the hypothesis that all Scl proteins are homotrimeric and cell wall-anchored. These proteins contain the rod-shaped collagenous domain proximal to cell surface, as well as a variety of outermost non-collagenous domains that generally lack predicted functions but can be grouped into one of six clusters based on sequence similarity. The well-characterized Scl1 proteins of S. pyogenes show a dichotomous switch in ligand binding between human tissue and blood environments. In tissue, Scl1 adhesin specifically recognizes the wound microenvironment, promotes adhesion and biofilm formation, decreases bacterial killing by neutrophil extracellular traps, and modulates S. pyogenes virulence. In blood, ligands include components of complement and coagulation-fibrinolytic systems, as well as plasma lipoproteins. In all, the Scl proteins signify a large family of structurally related surface proteins, which contribute to the ability of streptococci to colonize and cause diseases in humans and animals. This article is protected by copyright. All rights reserved.