Autism has a strong genetic and environmental basis in which inflammatory markers and factors concerned with synapse formation, nerve transmission and information processing such as brain-derived neurotrophic factor (BDNF), polyunsaturated fatty acids (PUFAs): arachidonic (AA), eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) and their products and neurotransmitters: dopamine, serotonin, acetylcholine, GABA (gamma-aminobutyric acid) and catecholamines and cytokines are altered. Anti-oxidants, vitamins, minerals and trace elements are needed for the normal metabolism of neurotrophic factors, eicosanoids and neurotransmitters, supporting reports of their alterations in autism. But, the exact relationship among these factors and their interaction with genes and proteins concerned with brain development and growth is not clear. It is suggested that maternal infections and inflammation and adverse events during intrauterine growth of the fetus could lead to alterations in the gene expression profile and proteomics that results in dysfunction of the neuronal function and neurotransmitters, alteration(s) in the metabolism of polyunsaturated fatty acids (PUFAs) and their metabolites resulting in excess production of pro-inflammatory eicosanoids and cytokines and a deficiency of anti-inflammatory cytokines and bioactive lipids that ultimately results in the development of autism. Recent studies revealed that various PUFAs and their metabolites influence the synthesis, release and action of various neurotransmitters, synapse formation and information processing in the brain. We also noted that PUFAs and their anti-inflammatory metabolites such as lipoxin A4 enhance the production of BDNF, a potent neurotrophic factor. In addition, PUFAs influence gut microbiota. These evidences suggest that altered PUFA metabolism has a significant role in the pathobiology of autism. In view of this, I propose that all pregnant women or those who are at high risk to have autistic children may be supplemented with AA, EPA and DHA and co-factors needed for their optimum metabolism such that anti-inflammatory lipoxin A4 and BDNF are produced in adequate amounts in the developing brain such that autism and other related disorders are prevented.