The long-duration response (LDR) to levodopa is an important component of the therapeutic response to the drug in Parkinson's disease (PD). Some characteristics are peculiar: it is independent from peripheral pharmacokinetics of levodopa, but it is dependent on the intervals between doses and on the size of each dose. Once the LDR fully develops, it is stable and maximal. After stopping treatment, the decay rate is inversely related to the severity of PD; when the LDR decreases over time, the patients present a fluctuating motor response. Therapeutic strategies based on the development and maintenance of the LDR should be sought to maximize the clinical benefit induced by levodopa and to avoid the appearance of motor complications.