Dual-specificity tyrosine-regulated kinases (DYRKs) comprise a family of protein kinases within the CMGC group of the eukaryotic kinome. Members of the DYRK family are found in 4 (animalia, plantae, fungi, and protista) of the 5 main taxa or kingdoms, and all DYRK proteins studied to date share common structural, biochemical, and functional properties with their ancestors in yeast. Recent work on DYRK proteins indicates that they participate in several signaling pathways critical for developmental processes and cell homeostasis. In this review, we focus on the DYRK family of proteins from an evolutionary, biochemical, and functional point of view and discuss the most recent, relevant, and controversial contributions to the study of these kinases.