The first non-immunoglobulin based framework for affinity proteins were described in 1995. The new molecules were called affibodies and were based on combinatorial protein engineering of the small and robust a-helical structure of protein A. Affibodies have since then found broad use as selective binding reagents in biotechnology applications incl. separomics, diagnostics and receptor blocking. Recently, systems based on affibodies labelled for fluorescence resonance energy transfer (FRET)-based detection have been developed to allow quantitative measurements of non-labelled target molecules for applications in for example protein “chip” formats. So-called anti-idiotypic affibodies have also been developed, suitable for Self-assembled Networks of Artificial Proteins (SNAP) to allow the build-up of molecular micro structures. Recently, the structure of an affibody-target co-complex was solved by both x-ray crystallography and NMR. These structure showed upon a high charge and structural complementarity in the binding interface, which had a size in comparity with antibody-antigen systems. In parallel to the use of phage display technology, new selection systems for affibody libraries have also been developed both based on Gram positive bacteria, FACS-sorting of micro beads and protein contact assays.