The actin gene family is highly conserved across eukaryotic species, and its family members share a high degree of protein sequence homology. Despite a wealth of knowledge on the structural and functional properties of actin in general, the distinct characteristics of the individual actin isoforms are only beginning to be understood. Recent animal models have provided considerable insight into the unique functions of the different actin isoforms. Additionally, evidence is emerging that the different isoforms have distinct structural and biochemical properties that likely relate to their unique functions. Furthermore, specific regulatory elements and nucleotide coding sequence differences are thought to confer functional specificity to the actin isoforms. Continued elucidation of the functional distinctions between actin isoforms will further our knowledge of the pathophysiology underlying actin-related diseases.