Dopaminergic neurons of the midbrain are the main source of dopamine (DA) in the mammalian central nervous system. Their loss is associated with one of the most prominent human neurological disorders, Parkinson's disease (PD). Dopaminergic neurons are found in a 'harsh' region of the brain, the substantia nigra pars compacta, which is DA-rich and contains both redox available neuromelanin and a high iron content. Although their numbers are few, these dopaminergic neurons play an important role in the control of multiple brain functions including voluntary movement and a broad array of behavioral processes such as mood, reward, addiction, and stress. Studies into the developmental pathways which are involved in the generation of dopaminergic neurons in the brain have led to the identification of several specific transcription factors including Nurr1, Lmx1b and Pitx3, all shown to be important in the development of the mesencephalic dopaminergic system. The selective degeneration of these dopaminergic neurons in the substantia nigra pars compacta leads to PD but the exact cause for this nigral cell loss is still unknown.