Development of motor fluctuations and dyskinesia characterizes the transition from the early to the advanced Parkinson stage. Current oral therapeutic strategies aim at increasing the number of levodopa administrations and extending its benefit by the association of enzyme blockers (MAO- and COMT-inhibitors) and dopamine agonists. However, as disease progresses, mobility becomes progressively dependent on levodopa absorption and plasma bioavailability, resulting in disabling motor complications. If patients continue to experience off time with functional impact on activities of daily living after best oral medication adjustments, implementation of infusion therapies with apomorphine or levodopa, and surgical techniques should be considered. Compared with pulsatile oral therapy implementation of apomorphine and levodopa infusion determines more continuous striatal dopamine receptors stimulation resulting in significant reduction of off-time and dyskinesia, particularly peak-dose. However, long-term experience with these treatments shows that motor complications are not abolished by continuous receptor stimulation suggesting that synaptic plasticity and connectivity changes are not easily reversed once they are established. Early intervention ideally would target patients as soon as motor complications begin rather than at late stage. Preliminary evidence from early deep brain stimulation or early pump treatment suggests that this is feasible but before it is implemented in clinical practice it would require a detailed cost-benefit analysis.