The symptoms of Parkinson's disease can become increasingly difficult to control as the disease advances. Levodopa remains the most efficacious therapy for symptomatic treatment. However, with long-term therapy motor and non-motor complications develop. There is now accumulating evidence that several factors - the progressive pathology of Parkinson's disease, the change in drug pharmacodynamics, and the pulsatile manner in which short-acting dopaminergic agents stimulate striatal dopamine receptors - are key contributors to the priming of the basal ganglia for induction of motor complications. In this paper, an overview of the different factors inducing motor fluctuations and the role of dopamine receptors stimulation is provided.