Actin is the most abundant protein in most eukaryotic cells and is highly conserved, participating in numerous protein-protein interactions. It exists in monomeric (G-actin) and filamentous (F-actin) forms, regulated by nucleotide hydrolysis, ions, and actin-binding proteins. Actin plays critical roles in cell motility, shape, polarity, transcription regulation, and muscle contraction. Pathogens often disrupt or hijack the actin cytoskeleton. This review summarizes the structures of G- and F-actin and discusses interactions that control their polymerization and disassembly. Actin has three main isoforms in vertebrates, differing by a few amino acids, primarily in the N-terminal region. Actin undergoes various post-translational modifications. Over 80 actin structures have been determined, including those in complexes with actin-binding proteins (ABPs) and small molecules. Despite variations in bound molecules or nucleotide states, the actin monomer maintains a similar conformation. Actin belongs to a structural superfamily that includes sugar kinases, hexokinases, and Hsp70 proteins. The actin monomer folds into two major α/β-domains, with the outer and inner domains located within the actin filament. These domains are referred to as small and large domains based on their apparent sizes in electron microscopy (EM) images. Actin is divided into four subdomains, with subdomains 1 and 3 being structurally related and subdomains 2 and 4 being insertions into subdomains 1 and 3, respectively. The actin monomer is flat, fitting into a rectangular prism of dimensions 55 Å × 55 Å × 35 Å. The two major domains of actin have relatively little contact, with the polypeptide chain passing twice between them. The upper cleft binds the nucleotide and associated divalent cation (Mg²⁺), while the lower cleft between domains 1 and 3 is lined by hydrophobic residues and serves as the major binding site for ABPs. The communication between the two clefts provides the structural basis for how nucleotide-dependent conformational changes modulate ABP binding and filament subunit contacts. G-actin is not an effective ATPase, whereas F-actin is. The differences between the ATP- and ADP-bound states involve two loops: the Ser14 β-hairpin loop and the sensor loop containing methylated His73. These loops engulf the phosphates of the nucleotide. Nucleotide-dependent conformational changes begin with Ser14, which in the ATP state makes a hydrogen-bonding contact with the γ-phosphate. After hydrolysis and γ-phosphate release, Ser14 changes orientation to form a hydrogen-bonding contact with the β-phosphate of the nucleotide. InActin is the most abundant protein in most eukaryotic cells and is highly conserved, participating in numerous protein-protein interactions. It exists in monomeric (G-actin) and filamentous (F-actin) forms, regulated by nucleotide hydrolysis, ions, and actin-binding proteins. Actin plays critical roles in cell motility, shape, polarity, transcription regulation, and muscle contraction. Pathogens often disrupt or hijack the actin cytoskeleton. This review summarizes the structures of G- and F-actin and discusses interactions that control their polymerization and disassembly. Actin has three main isoforms in vertebrates, differing by a few amino acids, primarily in the N-terminal region. Actin undergoes various post-translational modifications. Over 80 actin structures have been determined, including those in complexes with actin-binding proteins (ABPs) and small molecules. Despite variations in bound molecules or nucleotide states, the actin monomer maintains a similar conformation. Actin belongs to a structural superfamily that includes sugar kinases, hexokinases, and Hsp70 proteins. The actin monomer folds into two major α/β-domains, with the outer and inner domains located within the actin filament. These domains are referred to as small and large domains based on their apparent sizes in electron microscopy (EM) images. Actin is divided into four subdomains, with subdomains 1 and 3 being structurally related and subdomains 2 and 4 being insertions into subdomains 1 and 3, respectively. The actin monomer is flat, fitting into a rectangular prism of dimensions 55 Å × 55 Å × 35 Å. The two major domains of actin have relatively little contact, with the polypeptide chain passing twice between them. The upper cleft binds the nucleotide and associated divalent cation (Mg²⁺), while the lower cleft between domains 1 and 3 is lined by hydrophobic residues and serves as the major binding site for ABPs. The communication between the two clefts provides the structural basis for how nucleotide-dependent conformational changes modulate ABP binding and filament subunit contacts. G-actin is not an effective ATPase, whereas F-actin is. The differences between the ATP- and ADP-bound states involve two loops: the Ser14 β-hairpin loop and the sensor loop containing methylated His73. These loops engulf the phosphates of the nucleotide. Nucleotide-dependent conformational changes begin with Ser14, which in the ATP state makes a hydrogen-bonding contact with the γ-phosphate. After hydrolysis and γ-phosphate release, Ser14 changes orientation to form a hydrogen-bonding contact with the β-phosphate of the nucleotide. In