Therapeutic strategies in Parkinson's disease (PD) provide control of motor (nigral) and nonmotor (extranigral) symptoms. Nigral dopamine-related signs and symptoms are addressed by supplementation or substitution of cerebral dopamine, and extranigral nondopamine-related symptoms are treated by addressing specific autonomic, neuropsychiatric and sleep dysfunctions. However, the ultimate goal in treating PD is to slow, stop or modify disease progression through early and appropriate intervention. Recognition of the various nonmotor clinical manifestations of PD is critical to early diagnosis and treatment. Disease-modifying drugs, once identified, should be initiated as soon as possible, preferably in the prodromal (premotor) phase of the disease. In this review, clinical signs and symptoms of this phase will be described, as will the (suggested) criteria for diagnosis and optimal initiation of disease-modifying agents. Both symptomatic and disease-modifying agents applicable in the premotor phase of PD will also be addressed.