From time to time, paediatricians are confronted with children who might suffer from a primary immunodeficiency disease. For practical purposes, these children can be divided into four main clinical categories: (1) a relatively large group of children with recurrent ear-nose and throat and lower respiratory tract infections, in some cases caused by deficiencies of antibodies or complement; (2) children with failure to thrive, intractable diarrhoea or an opportunistic infection which can be caused by a T-lymphocyte or combined immunodeficiency; (3) children with infections with pyogenic bacteria or fungi as seen in case of granulocyte/monocyte function deficiency; and (4) a small heterogeneous group of children with recurrence of particular infections. Also, acquired immunodeficiency becomes a more common problem in paediatric practice. Flow cytometric immunophenotyping of leucocytes appears to be an efficient and rapid tool in the diagnosis and follow-up of immunodeficient patients, supporting early recognition, before serious infections have compromised the child's general condition. This technique can now be performed in many hospitals. In this review, we give directions for the use of flow cytometric immunophenotyping of leucocytes in the diagnosis and follow-up of immunodeficient children according to the four main clinical categories.