The neurodegenerative and neurotoxic aspects of schizophrenia and/or psychosis involve genetic, epigenetic, and neurotoxic propensities that impinge upon both the symptom domains and the biomarkers of the disorder, involving cellular apoptosis/excitotoxicity, increased reactive oxygen species formation, viral and bacterial infections, anoxic birth injury, maternal starvation, drugs of abuse, particularly cannabis, metabolic accidents, and other chemical agents that disrupt normal brain development or the integrity of brain tissues. Evidence for premorbid and prodromal psychotic phases, aspects of neuroimaging, dopamine, and psychosis vulnerability, and perinatal aspects provide substance for neurodegenerative influences. Not least, the agencies of antipsychotic contribute to the destructive spiral that disrupts normal structure and function. The etiopathogenesis of psychosis is distinguished also by disruptions of the normal functioning of the neurotrophins, in particular brain-derived neurotrophic factor, dyskinesic aspects, immune system disturbances, and metabolic aspects. Whether detrimental to neurodevelopment or tissue-destructive, or an acceleration of neurotoxic pathways, the notion of neurodegeneration in the pathophysiology of schizophrenia spectrum and psychotic disorders continues to gather momentum.