Depression is a frequent non-motor symptom of Parkinson's disease (PD), and may even precede the onset of motor symptoms of parkinsonism. Beyond its negative influence on mood and affection, depression in PD is frequently associated with other neuropsychiatric symptoms and with late- stage complications such as dementia. Despite its profound impact on quality of life and cognitive functioning in PD, depression in PD is often under-recognized and poorly treated. Pathophysiological studies demonstrated that depression in PD is associated with global dysfunction of interactions between discrete brain areas rather than focal structural or functional abnormalities, and that it is sustained by pathological changs of several neurotransmitter/receptor complexes. In general, all traditional antidepressants and some dopamine agonists have been found to be safe and well tolerated to treat depressive symptoms in PD, despite of initial warning on worsening of parkinsonism. Available data suggest that time-course of response differs among antidepressants. Efficacy results from clinical trials with antidepressant in PD are, however, rather uncertain, although pooled analysis suggests a moderate benefit. Several issues may critically impact the results of clinical trials with antidepressants in PD, including the correct psychiatric diagnosis, the overlap of symptoms between depression and PD, and the selection of appropriate end-points and rating scales.