Parkinson's disease (PD) is a neurodegenerative disorder whose pathogenesis depends on a combination of genetic and environmental factors. The aim of the present review was to provide an updated description of the findings emerging from prospective longitudinal cohort studies on the possible risk/protective factors underlying the development, progression and clinical subtypes of PD. We reviewed all the environmental, lifestyle, dietary, comorbid and pharmacological factors that have been investigated as possible modifiable protective/risk factors for PD by longitudinal studies. Only a few factors have the epidemiological evidence and the biological plausibility to be considered risk (pesticides, dairy products, β2-adrenoreceptor antagonists) or protective (smoking, caffeine and tea intake, physical activity, gout, vitamin E intake, non-steroidal anti-inflammatory drugs and β2-adrenoreceptor agonists) factors for PD. Caffeine intake and physical activity also seem to slow down the progression of the disease, thus representing good candidates for primary prevention and disease modifying strategies in PD. Possible modifiable risk factors of PD subtypes is almost unknown and this might depend on the uncertain biological and neuropathological reliability of clinical subtypes. The results of the present review suggest that only eleven risk/protective factors may be associated with the risk of PD. It may be possible to target some of these factors for preventive interventions aimed at reducing the risk of developing and the rate of progression of PD.