Over the last decade the genetic defect in nearly all of the well described primary immunodeficiency conditions have been identified, thereby allowing a molecular diagnosis to be assigned to affected individuals. Current gene screening and direct sequencing techniques remain the gold standard for determining the precise defect and allow for further ascertainment of carrier status and antenatal diagnosis. However, these techniques are time consuming and labour intensive. This has led to the development of protein based screening tools for a number of primary immunodeficiency syndromes. These assays have a high level of specificity and sensitivity and can be used as a first line test for determining the molecular diagnosis.