Parkinson's disease (PD) is the most common movement disorder associated with the elderly which, other than symptomatic therapies, has no effective treatment or preventive measures. Sirtuins and their pharmacological activators/inhibitors have been associated with a range of neuroprotective effects, and a large body of work on sirtuins' influence on PD pathology has accumulated over the past decade. Here, evidence for sirtuins' activities as modifiers of PD pathology and how the mammalian sirtuin paralogues may have conflicting impacts on PD pathogenesis and disease progression is reviewed. The possible cellular and molecular mechanisms underlying sirtuin activities in PD are discussed in the light of current knowledge with reference to autophagy, mitochondrial homeostasis, and microtubule dynamics. (C) 2016 Wiley Periodicals, Inc.