The loss of dopamine (DA)-producing neurons in the substantia nigra pars 
compacta (SN) underlies the core motor symptoms of the progressive movement 
disorder Parkinson's disease (PD). To date, no treatment to prevent or slow SN 
DA neurodegeneration exists; thus, the identification of the underlying factors 
contributing to the high vulnerability of these neurons represents the basis for 
the development of novel therapies. Disrupted Ca2+ homeostasis and mitochondrial 
dysfunction seem to be key players in the pathophysiology of PD. The autonomous 
pacemaker activity of SN DA neurons, in combination with low cytosolic Ca2+ 
buffering, leads to large somatodendritic fluctuations of intracellular Ca2+ 
levels that are linked to elevated mitochondrial oxidant stress. L-type 
voltage-gated Ca2+ channels (LTCCs) contribute to these Ca2+ oscillations in 
dendrites, and LTCC inhibition was beneficial in cellular and in vivo animal 
models of PD. However, in a recently completed phase 3 clinical trial, the 
dihydropyridine (DHP) LTCC inhibitor isradipine failed to slow disease 
progression in early PD patients, questioning the feasibility of DHPs for PD 
therapy. Novel evidence also suggests that R- and T-type Ca2+ channels (RTCCs 
and TTCCs, respectively) represent potential PD drug targets. This short review 
aims to (re)evaluate the therapeutic potential of LTCC, RTCC, and TTCC 
inhibition in light of novel preclinical and clinical data and the feasibility 
of available Ca2+ channel blockers to modify PD disease progression. I also 
summarize their cell-specific roles for SN DA neuron function and describe how 
their gating properties allow activity (and thus their contribution to stressful 
Ca2+ oscillations) during pacemaking.