The present invention relates to improved Nanobodiesâ„¢ against Tumor Necrosis Factor-alpha (TNF-alpha), as well as to polypeptides comprising or essentially consisting of one or more of such Nanobodies. The invention also relates to nucleic acids encoding such Nanobodies and polypeptides; to methods for preparing such Nanobodies and polypeptides; to host cells expressing or capable of expressing such Nanobodies or polypeptides; to compositions comprising such Nanobodies, polypeptides, nucleic acids or host cells; and to uses of such Nanobodies, such polypeptides, such nucleic acids, such host cells or such compositions, in particular for prophylactic, therapeutic or diagnostic purposes, such as the prophylactic, therapeutic or diagnostic purposes.La presente invención se refiere a un dominio variable de inmunoglobulina aislado que se enlaza a TNFa, el domino que comprende cuatro regiones de estructura (FR1 a FR4) y 3 regiones que determinan la complementariedad (CDR1 a CDR3), en donde: a. CDR1 comprende la secuencia de aminoácidos (SEC ID NO: 193); b. CDR2 comprende la secuencia de aminoácidos (SEC ID NO: 261); y c.CDR3 comprende la secuencia de aminoácidos (SEC. ID NO: 239).