Levodopa combined with a peripheral dopa decarboxylase inhibitor continues to be the primary treatment for Parkinson's disease. Since levodopa has a short half-life, immediate release levodopa preparations lead to a rapid increase and subsequent decrease of plasma levodopa concentrations. This pharmacokinetic profile is at least partially responsible for the reduced efficacy and fluctuating motor response that is often seen with long term treatment. Two sustained release levodopa formulations (carbidopa/levodopa and benserazide/levodopa) have been developed to aid management of motor fluctuations. These preparations provide smoother pharmacokinetic profiles, with levodopa concentrations sustained substantially longer than with the immediate release formulations.Clinical trials have demonstrated the superior efficacy of sustained release carbidopa/levodopa (Sinemet®CR) compared with conventional, immediate release carbidopa/levodopa. Most patients with Parkinson's disease who convert from immediate release to sustained release carbidopa/levodopa show improvement in disease symptoms. While sustained release carbidopa/levodopa does not eliminate motor fluctuations, it provides good maintenance of global motor response (ratio of time ‘on’ to ‘off’) for extended time periods.Conversion from immediate to sustained release formulations is beneficial to patients with a wide range of disease severity. Conversion success is not dependent on patient demographic variables. However, the effort and time required for conversion relate clinically to disease severity.Sustained release benserazide/levodopa releases levodopa for several hours longerin vitrothan the immediate release formulation. Reports of clinical trials, although somewhat mixed, are generally encouraging. Neither of the 2 formulations of benserazide/levodopa is currently available in the US.