Among the most notable wins during that streak were a fourth-round knockout on 19 October 1990, of Alfonzo Redondo, which gave Castillejo the Spanish Welterweight Championship, at Leganés.

On 10 April 1992, Castillejo got his first win when he knocked out former IBF lightweight champion, Puerto Rican Harry Arroyo, in three rounds at Leganes.

On 12 December of that year, Castillejo added the WBC's Mundo Hispano light middleweight title, when he defeated Enrique Areco by a twelve-round decision in Oviedo.

After defending his Mundo Hispano regional title with success in a rematch with Victor Hugo Sclarandi on 29 October of that year by a knockout in five rounds, Castillejo finally had his first fight abroad when he beat Bernard Razzano by a knockout in six rounds, at Dijon, France, to conquer the European light middleweight title.

He defended the title successfully four times, then lost it, on 3 January 1995 to the then WBA light middleweight champion Laurent Boudouani, in Épernay, France, by knockout in the ninth round.

Castillejo lasted the twelve round distance with De La Hoya, but was sent to the canvas seconds before the fight ended, and lost a unanimous twelve-round decision and his world title, on 23 June 2001.

After six months, Castillejo returned to the boxing ring, beating the well regarded Xavier Moya by a knockout in five rounds, On 11 January 2002, to win the vacant European Community's Junior Middleweight title, in Barcelona.

This interim recognition was later retired from him, however, because he did not fight the WBC's recognized champion, which at the time was Shane Mosley, who had suffered an injury and was unable to box for the period being.

On 15 July 2006, Castillejo sprang back on the boxing scene by defeating younger Felix Sturm of Germany to seize the WBA middleweight belt in an exciting fight.