Receptor-mediated phagocytosis is a complex process that mediates the internalization, by a cell, of other cells and large particles; this is an important physiological event not only in mammals, but in a wide diversity of organisms. Of simple unicellular organisms that use phagocytosis to extract nutrients, to complex metazoans in which phagocytosis is essential for the innate defence system, as a first line of defence against invading pathogens, as well as for the clearance of damaged, dying or dead cells. Evolution has armed multicellular organisms with a range of receptors expressed on many cells that serve as the molecular basis to bring about phagocytosis, regardless of the organism or the specific physiological event concerned. Key to all phagocytic processes is the finely controlled rearrangement of the actin cytoskeleton, in which Ca(2+) signals play a major role. Ca(2+) is involved in cytoskeletal changes by affecting the actions of a number of contractile proteins, as well as being a cofactor for the activation of a number of intracellular signalling molecules, which are known to play important roles during the initiation, progression and resolution of the phagocytic process. In mammals, the requirement of Ca(2+) for the initial steps in phagocytosis, and the subsequent phagosome maturation, can be quite different depending on the type of cell and on the type of receptor that is driving phagocytosis. In this review we discuss the different receptors that mediate professional and non-professional phagocytosis, and discuss the role of Ca(2+) in the different steps of this complex process.