The completion of the Human Genome Project has provided insight into human genetic variation, most commonly represented by single-nucleotide polymorphisms. There is presently a great deal of interest in linking genetic and phenotypic variation in the form of severity of, and susceptibility to, common multifactorial diseases. This article provides a background to recent advances in genetics, focusing on the application to common neonatal disorders and the practical difficulties of genetic association studies, as well as highlighting the potential impact on clinical practice.