Identification of the smallest antibody fragment still capable of binding to antigen has progressed from full antibody molecules to Fab and recombinant single chain Fv fragments. Now, a further reduction to single domain binding proteins based upon immunoglobulin VH and VH-like domains offers exciting prospects in the development of novel immunotherapeutics and immunodiagnostics. Minimisation of the antigen-binding fragment to such small single-domain proteins offers the advantages of enhanced stability, and possibly access to a class of antigenic epitopes not generally recognised by conventional antibodies.