Although the advent of monoclonal antibody technology in the 1970s provided the means to specifically target radioisotopes to tumours, the initial clinical evaluations of radioimmunotherapy (RAIT) were largely unsuccessful. Over the past few decades, molecular biology techniques have advanced sufficiently to allow scientists to re-engineer antibodies to address the factors that were believed to be responsible for the failures of the early radioimmunotherapy trials. This review addresses the recent advances in antibody engineering and in RAIT strategies that have brought this field to the brink of success.