Microarray analysis has become a widely available tool for the generation of gene expression data on a genomic scale. Since the studies with similar protocols are growing, it has become necessary to systematically revise the large body of literature to decipher the gene expression data. In this review, we analyzed and critically discussed the database presented from 14 published studies that showed the gene expression profile in heart failure (HF) using microarray as a primary tool. After comparing the diverse database from these studies, we explain the protein translational, matri-cellular, immunological and fibrosis-related mechanisms in HF. In addition to previously annotated genes, we analyzed two differentially expressed expressed sequence tags (ESTs) (KIAA0152 and Suppressor of G(Two) allele of the suppressor of kinetochore protein-1, SGT1) in HF and showed how bio-informatic analysis of ESTs can lead to the identification of novel pathways active in HF. We have also discussed the new publicly accessible tools that link the gene expression data to gene ontogeny (GO) and functionality. Finally, we have systematically revised the chromosomal localization of the genes that are specifically up-regulated in HF. We have thus spotted chromosome 1, 2, 11 and 12 as the chromosomal hotspots of HF. This methodical approach will simplify the existing concepts on the evolution and progression of HF and lead us toward the development of newer diagnostic and therapeutic tools. Although modeled to HF, this approach should be of broader scientific interest to elaborate multiple genes and complex pathways.