Parkinson’s disease (PD) is a debilitating neurodegenerative disease that affects millions of people around the world. PD patients suffer from major symptoms including tremors during rest, muscular rigidity, slowness in the movement and loss of balance. The disease slowly progresses over the years and currently none of the medications is known to cure the disease. Several aetiological factors have been proposed for PD, including environmental toxins, endogenously produced toxic tetrahydroisoquinolines and few genetic mutations, but the pathways leading to dopaminergic neuron death are still not clearly understood. Increased concentrations of MPTP-like toxins i.e., salsolinol and  1-benzyl-1,2,3,4-tetrahydroisoquinoline are identified as endogenous neurotoxins in PD brains. These neurotoxins have been proven to be deleterious to dopaminergic neurons in cell culture models of PD. Several studies demonstrated that mitochondrial dysfunction, oxidative stress and protein aggregation are the key players in the pathogenesis of PD. However, the exact interrelationship between mitochondrial complex I deficiency, oxidative stress and dopamine neuron death is poorly understood.  Although the specificity of dopamine neuron death in PD is not known, several studies indicate that dopamine transporters, vesicular monoamine transporters, and in some cases dopamine itself seems to play important role on the death of dopamine neurons in PD. Recent developments shed light on explaining some of the pathogenic mechanisms involved in PD. For example, alpha-synuclein transgenic animal models provided evidence that overexpression of wild type alpha-synuclein or its mutant form (A53T) can induce inclusion formation and neurodegeneration in mice and flies. More importantly, post-translational modifications in alpha-synuclein by oxidative stress may be responsible for alpha-synuclein aggregation and neurodegeneration. Additional studies also indicate that inflammation may also play a role in the neurodegeneration. We suggest that future neuroprotective therapies for PD would be a combination of free radical scavengers, anti-inflammatory compounds and neurotrophic factors like GDNF and IGF-I. By reducing oxidative stress and inflammatory responses, and inhibiting apoptotic signaling pathways these molecules may avert apoptosis and hence protect dopaminergic neurons in PD.