The IQ motif is widely distributed in both myosins and non-myosins and is quite common in the database that includes more than 900 Pfam entries. An examination of IQ motif-containing proteins that are known to bind calmodulin (CaM) indicates a wide diversity of biological functions that parallel the Ca2+-dependent targets. These proteins include a variety of neuronal growth proteins, myosins, voltage-operated channels, phosphatases, Ras exchange proteins, sperm surface proteins, a Ras Gap-like protein, spindle-associated proteins and several proteins in plants. The IQ motif occurs in some proteins with Ca2+-dependent CaM interaction where it may promote Ca2+-independent retention of CaM. The action of the IQ motif may result in complex signaling as observed for myosins and the L-type Ca2+ channels and is highly localized as required for sites of neuronal polarized growth and plasticity, fertilization, mitosis and cytoskeletal organization. The IQ motif associated with the unconventional myosins also promotes Ca2+ regulation of the vectorial movement of cellular constituents to these sites. Additional regulatory roles for this versatile motif seem likely.