Rapidly expanding genomic information offers important insights into the mechanisms of acquired immunity and has fostered progress in comparative immunology. However, the question of why the acquired immune system, a trait restricted to jawed vertebrates, evolved has rarely been addressed. Here, I will examine three unique features of early vertebrate evolution, during the 50 million years when the acquired immune system evolved: co-evolution with specialised parasites, increased metabolic rates and genomic instability. These combine to shape a powerful multi-level and multi-causal selective scenario that I propose could have moulded the acquired immune system.