Intrinsically disordered regions (IDRs) perform a vast repertoire of essential functions across organisms in all kingdoms of life and, in many cases, function by driving the formation of biomolecular condensates. Recent studies have unveiled significant differences in the evolution of structured regions and IDRs and the challenges associated with employing existing bioinformatic tools to study IDR evolution. Elucidating the sequence determinants underlying the diverse functions of IDRs remains a challenge. In this chapter, we discuss the evolution of IDRs versus structured regions, their role in the origin of life, and their involvement in the evolution of biomolecular condensates. We highlight examples demonstrating how IDRs exert conserved functions across organisms and discuss the challenges inherent in systematically analyzing sequence-function relationships within IDRs. Additionally, we review emerging methods developed to address these challenges.