With the advent of second generation sequencing technologies after mid of decade 2000, entire field of sequencing, annotation and our understanding of a functioning system has changed for positive, drastically, economically and scientifically. However, the field is still under revolutionary changes and almost every year we are witnessing continual improvement and advancements. During the era of human genome project, the cost of sequencing was as high as $10 per base with traditional capillary sequencing. Later on it was further improved through introduction of shotgun sequencing and novel bioinformatics algorithms to detect the confidence on sequence quality. The read lengths could go in kilobase. However, the cost still remained very high and technology remained restricted to few rich labs. In finishing a human genome, with five pioneering countries, it took more than 10 years and millions of dollars. It can be well-imagined that what could happen if we have to sequence the genome of approximately estimated total 30 million species on earth! Leaving aside the genome of various species, scientists after finishing human genome aimed to develop tailor made drugs based on genome information. However, this requires personal genome sequencing, knowledge of genome level SNPs and other variations. More to add, there were some very serious domains of life about which our knowledge remained very limited and full of myths till the arrival of application of next generation sequencing.