Actin, one of the main proteins of muscle and cytoskeleton, exists as a variety of highly conserved isoforms whose distribution in vertebrates is tissue-specific. Synthesis of specific actin isoforms is accompanied by their subcellular compartmentalization, with both processes being regulated by factors of cell proliferation and differentiation. Actin isoforms cannot substitute for each other, and the high-level synthesis of exogenous actins leads to alterations in cell organization and morphology. This indicates that the highly conserved actins are functionally specialized for the tissues in which they predominate. The first goal of this review is to analyze the data on the polymerizability of actin isoforms to show that cytoskeleton isoactins form less stable polymers than skeletal muscle actin. This difference correlates with the dynamics of actin microfilaments versus the stability of myofibrillar systems. The three-dimensional actin structure as well as progress in the analysis of conformational changes in both the actin monomer and the filament allows us to view the data on the structure and polymerization of isoactins in terms of structure-function relationships within the actin molecule. Most of the amino acid substitutions that distinguish actin isoforms are located apart from actin-actin contact sites in the polymer. We suggest that these substitutions can modulate the ability of actin monomers to form more or less stable polymers by long-range (allosteric) regulation of the contact sites.