Parkinson's disease (PD) is characterized by the selective loss of dopamine (DA) neurons in the substantia nigra compacta (SNc). The transcription factor Pitx3 is important for the differentiation and maintenance of midbrain DA neurons during development. There is highly restricted and constitutive expression of Pitx3 in the SNc and ventral tegmental area (VTA) of the midbrain after birth. In addition to its importance during development, Pitx3 also has roles in the long-term survival and maintenance of the midbrain DA neurons. In this review, we discuss the function of Pitx3 throughout the life of midbrain neurons and the contribution of Pitx3 to disease mechanisms.