There is increasing evidence to challenge the traditional view that the initiation of drug treatment in Parkinson's disease (PD) should be delayed until the patient has significant disability such as to affect work or social function. Firstly, to delay treatment sentences the patient to protracted impairment of quality of life that could be improved by therapy. Secondly, there is evidence to support the notion that earlier rather than later initiation of treatment leads to better long term motor benefit. The selection of which drug to begin must be tailored to the patient's individual characteristics and circumstances. Monoamine oxidase B inhibitors result in a mild improvement in motor function compared to dopamine agonists or levodopa. They are well tolerated, easy to use once a day drugs and there is evidence that early use of Rasagiline improves motor outcome. Dopamine agonists lead to a substantial improvement in motor function and are, or will shortly be, available as once a day drugs. They are generally well tolerated but can be associated with exacerbating confusion or hallucinations and with behavioral changes. Levodopa is the most potent of the dopaminergic drugs. It is routinely combined with a dopa decarboxylase inhibitor and can also be used with a catecholo-o-methyl transferase inhibitor for enhanced absorption. The most important limiting factor for the use of levodopa is the emergence of motor complications. These are related to a number of factors including the dose of levodopa and the duration of its use. Ann Neurol 2008;64 (suppl):S47–S55