This chapter reviews general aspects of the normal human haemoglobins which include those predominantly present in the embryo, the fetus and newborn baby, and in the normal adult. Special emphasis is given to factors which affect the levels of fetal haemoglobin in the adult because increased percentages of Hb F can be of great benefit to adults with certain haemoglobinopathies such as sickle cell anaemia and beta-thalassaemia. A review of the numerous Hb variants published since the discovery of Hb S in 1959 reveals a steady stream of newly detected abnormalities; most of these are the result of single-point mutations in the alpha-, beta-, gamma-, or delta-globin genes. Of the more than 600 variants listed in a repository, some 200 have clinical significance because of a decreased stability, a change in functional properties, among others. Methodology developed for the detection and quantitation of normal and abnormal Hb components has been greatly modified during the past 30 years; isoelectrofocusing and different fast developing micro chromatographic procedures are the methods of choice. Analyses of DNA isolated from the white cells has become most useful for the final characterization of the variants; this methodology consists of amplification of a desired segment of DNA and identification of a mutation with labelled oligonucleotide probes. Additional methods include sequence determination of this amplified DNA and identification of known mutations with an allele specific amplification procedure.