Current pharmacological interventions for the treatment of patients in the early stages of Parkinson’s disease (PD) target the dopaminergic system and are particularly effective at targeting motor symptoms. The dopamine precursor levodopa is the most commonly used agent, and dopamine receptor antagonists are increasingly used. As the disease progresses, the length of time where levodopa is effective shortens, leading to prolonged “off-periods” where motor symptoms reappear or debilitating side effects arise. To counteract this reduction in efficacy co-administration of levodopa together with dopaminergic enzyme blockers, such as monoamine oxidase-B and catechol-O-methyl transferase inhibitors, prolongs its action and thereby reduces the duration of off-periods. Recent evidence indicates that non-dopaminergic agents represent novel therapeutic options for PD, including adenosine A2A antagonists, cannabinoids, zonisamide and trophic factors.