The present invention relates to protein and polypeptide constructs that comprise single variable domains that are linked to an Fc portion. The immunoglobulin constructs comprise two polypeptide chains in which each polypeptide chain comprises two or more single variable domains that are linked, usually via a suitable hinge region or linker, to one or more constant domains that, together, form an Fc portion. The invention also relates to polypeptide chains that form part of such constructs and/or that can be used to form such constructs. The invention further relates to nucleotide sequences and nucleic acids that encode or can be used to express such constructs or polypeptide chains; to methods for producing such constructs and polypeptides chains; to compositions (and in particular pharmaceutical compositions) that comprise such constructs or polypeptide chains; and to uses of such constructs, polypeptide chains or compositions.