The response to dopamine replacement therapy in patients with degenerative parkinsonism is variable. Reasons for a poor therapy response include the type of parkinsonism, comorbidities, and differential effects on clinical features. An additional explanation, which has received much less attention, is sub-optimal therapy compliance. Single and multicentre studies of therapy compliance report significant under- and overuse of dopamine replacement therapy resulting in poor symptomatic control, or features of the dopamine dysregulation syndrome or other signs of dopaminergic excess (dyskinesia, confusion, visual hallucinations). In this article, the evidence for sub-optical adherence in Parkinson's disease (PD) is reviewed, and factors associated with sub-optimal compliance were examined, with two case vignettes to illustrate clinical consequences of deviation from the prescribed therapy regimen.