Remodeling of the actin cytoskeleton in cells is tightly regulated by a vast number of actin-binding proteins (ABPs). These proteins interact with actin via a limited set of conserved folding motifs. One of the most abundant actin-binding motifs is the beta-thymosin fold, represented by the prototypical actin-monomer sequestering protein thymosin-beta4. Among many cytoskeletal proteins, the beta-thymosin fold adopts a shorter form, known as the WASP homology domain 2. Some characteristic features of the beta-thymosin/WH2 fold include its small size (17-43 aa), significant sequence and length variability, frequent occurrence in the form of tandem repeats, and remarkable multifunctionality. This paper discusses the relationship between structure and function of the beta-thymosin/WH2 fold on the basis of four examples: (1) actin monomer sequestration (thymosin-beta4), (2) actin filament nucleation (WASP-Arp2/3 complex, Lmod, and spire), (3) actin filament elongation (Ena/VASP), and (4) cytoskeleton scaffolding (IRSp53 and MIM). Although the core function of the beta-thymosin/WH2 domain in all these proteins is actin binding, specific changes in the sequence of the domain and modular organization of the proteins in which it is found give rise to diverse functions in the regulation of actin cytoskeleton dynamics.