Actin filament formation plays a pivotal role in the development, regeneration and modulation of the morphologies and physiological functions of subcellular compartments and entire cells. All of these processes require tight temporal and spatial control of F-actin assembly. Recent work has shed new light on the control of actin filament formation by Ca2+ as very fast, transient messenger allowing for defined responses to signal intensities spanning several orders of magnitude. Recent discoveries highlight that a small but rapidly growing set of actin nucleators and related proteins, i.e. factors that have the power to promote the formation of new actin filaments in cells, are tightly controlled by the Ca2+ sensor protein CaM. We here review the cellular functions and the molecular mechanisms that couple Ca2+ signaling to the cytoskeletal functions of these factors. This set of proteins currently includes one actin nucleator of the formin family (INF2), the WH2 domain-based actin nucleator Cobl and its ancestor protein Cobl-like as well as fesselin/synaptopodin-2/myopodin and myelin basic protein (MBP). Considering the mechanistic principles of Ca2+ control of actin filament formation unveiled thus far and the diverse cell biological processes involving Ca2+ signaling it is obvious that our understanding of the cell biological crosstalk of Ca2+ transients with the in part highly specialized actin cytoskeletal structures observed in different cell types is only at its infancy. (C) 2018 Elsevier Inc. All rights reserved.