Schizophrenia is a psychiatric disorder of insufficiently clarified etiology. Neurodegenerative theory is based on the fact that schizophrenia is characterized by chronic and progressive processes in nervous system which are marked by the biochemical changes, altered histopathologic results, decline in brain functions and behavioral deterioration. Principal evidence of this theory is demonstrated by the morphometric analyses, which can prove volume reduction of cortex in many different brain regions, as well as enlargement of brain ventricles. As for the white matter changes, reduction in trajectories connecting prefrontal and temporal lobes has been observed. Measurements with the fMRI method have identified weaker global connectivity in patients with schizophrenia compared to healthy controls. Neurodegenerative theory is often connected with elevated levels of dopamine which in turn lead to inhibition of respiratory enzymes in mitochondria finally causing cell damage and death. This theory is also linked with hypofunction of NMDA receptors and consequentially raised levels of glutamate, a neurotransmitter which has an exotoxic effect and thus mediates further neurodegeneration. Results of numerous studies of cognitive function are taken as the most prominent critique of this theory. These studies confirm the absence of neurocognitive decline, even improvement in remission phase. Another significant critique is gliosis as the most important indicator of neurodegeneration, which has never been confirmed with certainty in patients with schizophrenia. Finally, neurodegenerative theory is connected with the majority of other theories in etiology of schizophrenia. It is also important to emphasize that connection of nerodevelopmental and neurodegenerative theories opens up a new progressive model.