The concept of schizophrenia as a neurodegenerative disorder has a long and somewhat controversial past. The absence of a histopathological phenotype in schizophrenia has been cited as evidence against a neurodegenerative hypothesis. However, studies of schizophrenia increasingly demonstrate subtle yet consistent histopathological deficits in addition to evidence of progressive clinical and neuroimaging findings. It is believed that schizophrenia can be considered as a limited neurodegenerative disorder with neurodevelopmental antecedents. Studies from clinical, neurocognitive, neuroimaging, and neuropathological domains are reviewed in critical analysis of this hypothesis. The conclusion is increasingly supported by neuroimaging studies that find progressive neurostructural changes, especially in gray matter content and ventricle size, and studies that report limited progression of clinical symptoms and neurocognitive function. Future studies utilizing high-resolution neuroimaging and sophisticated neuropsychological testing techniques will undoubtedly provide greater insight on the timing, regionality, and degree of progression in the early stages of schizophrenia.