AbstractParkinson disease (PD) is the second most common neurodegenerative disease after Alzheimer disease. Although PD has a relatively narrow clinical phenotype, it has become clear that its etiological basis is broad. Post‐mortem brain analysis, despite its limitations, has provided invaluable insights into relevant pathogenic pathways including mitochondrial dysfunction, oxidative stress and protein homeostasis dysregulation. Identification of the genetic causes of PD followed the discovery of these abnormalities, and reinforced the importance of the biochemical defects identified post‐mortem. Recent genetic studies have highlighted the mitochondrial and lysosomal areas of cell function as particularly significant in mediating the neurodegeneration of PD. Thus the careful analysis of post‐mortem PD brain biochemistry remains a crucial component of research, and one that offers considerable opportunity to pursue etiological factors either by ‘reverse biochemistry’ i.e. from defective pathway to mutant gene, or by the complex interplay between pathways e.g. mitochondrial turnover by lysosomes. In this review we have documented the spectrum of biochemical defects identified in PD post‐mortem brain and explored their relevance to metabolic pathways involved in neurodegeneration. We have highlighted the complex interactions between these pathways and the gene mutations causing or increasing risk for PD. These pathways are becoming a focus for the development of disease modifying therapies for PD. image Parkinson's is accompanied by multiple changes in the brain that are responsible for the progression of the disease. We describe here the molecular alterations occurring in postmortem brains and classify them as: Neurotransmitters and neurotrophic factors; Lewy bodies and Parkinson's‐linked genes; Transition metals, calcium and calcium‐binding proteins; Inflammation; Mitochondrial abnormalities and oxidative stress; Abnormal protein removal and degradation; Apoptosis and transduction pathways.This article is part of a special issue on Parkinson disease.