Calmodulin (CaM) is a major intracellular receptor for Ca2+. CaM is thus a crucial receptor to consider in pharmacological modification of cellular activity. Potential mechanisms by which drugs may modify CaM effectiveness are considered in the context of its interaction with Ca2+ and in turn with its various effectors. Some examples of established drug mechanisms are considered. A wide range of chemical compounds representing diverse pharmacological classes are anti-CaM under some conditions. No simple relationships have been established between molecular level events and therapeutic applicability of anti-CaM compounds.