There are still insufficient data on the natural course of Parkinson's disease (PD) owing to lack of standardized longitudinal follow-up studies. Reported progression rates in early PD vary considerably by a factor of 2 to 3. Similarly, data from sequential [18F]dopa PET studies in PD patients have produced variable decline rates of PET indices ranging between 7 and 70% per decade. Risk factors for rapid progression include old age at onset, concomitant major depression, dementia, and akinetic-rigid symptom presentation. The introduction of levodopa into the routine treatment of PD patients had a dramatic impact on symptomatic control without affecting the underlying rate of disease progression. By contrast, monoamine oxidase (MAO) B inhibition by deprenyl monotherapy in early PD was shown to delay the need for levodopa by around 9 months. However, the neuroprotective action disappeared after 2 years of follow-up. Furthermore, deprenyl also failed to influence the subsequent development of levodopa-induced motor complications. Available studies on mortality in PD provide heterogeneous mortality rates, probably because of discrepancies between patient populations with respect to co-morbidity, disease stage at study entry, and diagnostic accuracy. However, the most recent follow-up from the DATATOP cohort suggests normal life expectancy in carefully selected patients without significant co-morbidity and with adequate treatment and expert follow-up.