Cultured skin fibroblasts, among other non-neuronal cells (e.g. platelets, lymphocytes, red blood cells), provide an advantageous system for investigating dynamic molecular regulatory processes underlying abnormal cell growth, metabolism, and receptor-mediated signal transduction, without the confounding effects of disease state and its treatment in a variety of brain disorders, including schizophrenia, and are useful for studies of systemic biochemical defects with predominant consequences for brain function. These cells are also useful for studying aspects of neurotransmitter functions because the cells express enzymes involved in their metabolism, as well as their receptors with complete machinery for signal transduction. These processes also function predictably with receptors that are transfected in fibroblasts. This review will focus on the use of cultured skin of which have also been studied in post-mortem brains. These mechanisms might involve DNA processing and mitogenesis, cell-cell adhesion molecules, actions of growth factors, oxidative damage, and membrane phospholipid derived second messengers. This review will further discuss the implications of these processes to clinical and structural brain abnormalities. An understanding of these biochemical processes might help establish therapeutic implications and identify the risk for illness through experimental strategies such as epidemiology, family pedigree and high risk populations. Finally, despite some methodological limitations, skin fibroblasts are relatively easy to grow and maintain as primary cultures or as immortalized cell lines for long periods of time for use in investigating newly identified biochemical abnormalities.