Synthesis of genome level expression data related to human epilepsy and animal models of epileptogenesis is a challenge because of differences in the use of animal species and strains, brain regions, methods to trigger epileptogenesis, tissue sampling time-points, epilepsy phenotype assessment, array platforms, normalization algorithms, cutoff points for identifying differentially expressed genes etc. Nevertheless, a comprehensive review of reported analysis identifies chemokine signaling and toll-like receptor signaling as convergent epileptogenic pathways. This transcriptomic evidence is supported by genome-wide association analysis in epilepsy, known effect of small molecules on gene expression, and cellular and molecular studies. The present review thus demonstrates that synthesis of diverse genome level expression analysis in complex brain disorders can identify promising leads in understanding the mechanisms underlying them.