Life on earth exists in most diverse physical environments including extremes of temperature, pressure, salinity and pH or combination of these. These environments have been successfully colonized by numerous microorganisms, in particular bacteria, collectively called "extremophiles". Despite the deleterious effects of environment, they not only survive but also grow optimally. Despite abundant cold environments on earth’s surface, psychrophiles (Cold lovers) have received less attention than their warmer cousins (Thermophiles) but, in recent years, the study of psychrophiles has intensified. The focal theme of this book is to investigate psychrophilic proteins with their homologous thermophilic proteins to pin point sequence-structural differences and their relative evolutionary origin with respect to their mesophilic homologues. This study should summarize our initial efforts to delineate molecular adaptation features in the psychrophilic proteins. Phylogenetic study of homologous proteins should improve our understanding of the evolutionary divergence between psychrophiles and thermophiles.