Levodopa is the most effective drug available for the symptomatic treatment of Parkinson's disease (PD) and is the gold standard with which other therapies must be compared. Levodopa improves most parkinsonian symptoms and is associated with an apparent decrease in mortality rate. However levodopa usage is also associated with both acute and chronic side effects which compromise treatment. Levodopa is metabolized by both decarboxylase and catechol-O-methyl transferase enzymes. It is routinely administered in combination with a decarboxylase inhibitor to prevent the peripheral accumulation of dopamine and associated side effects such as nausea and vomiting. More recent studies suggest that combination of levodopa with an inhibitor of catechol-O-methyl transferase prolongs the duration of effect of the drug and can prolong the duration of motor response in fluctuating patients. This article will review the safety and efficacy of levodopa treatment.