The important element nitrogen can be fixed by symbiotic as well as asymbiotic nitrogen fixers to make it available as nutrient in the ecosystem. Symbioses with higher plants offer an ecological niche for a particular microorganism to fix nitrogen. Although there have been significant advances in nitrogen fixation research, the development of bioinformatics has opened a new window for providing novel understanding into the mechanism. The accessibility of complete genome sequences of symbiotic diazotrophs became a stepping stone for gaining insights into the working principle of bacterial cell. Studies on diazotrophs genomes exposed new evidences pertaining to evolution, structure, interactions between plants and microbes and diversity amongst them. Detection of a number of symbiotic genes associated with nitrogen fixation has strengthened functional genomic research. Accessibility of new software tools for genomic and proteomic analysis have accelerated research in the areas of codon usage, proteome analysis, molecular modeling and phylogenetic analysis of nitrogen fixation genes. In the present review we highlight the discovery of nitrogen fixation, research trends in nitrogen fixation in the pre-genomic era, the implications of bioinformatics research on nitrogen fixation, post-genomic research on BNF with special reference to synonymous codon usage analysis, proteome analysis, analysis of the molecular phylogeny of nitrogen fixation using nucleotide triplet based condensed matrix methods and the ambiguities in alignment based methods and use of homology modeling techniques in the structural biology of nitrogenases.