Living organisms have evolved to contain a wide variety of receptors and signaling pathways that are essential for their survival in a changing environment. Of these, the phosphoinositide pathway is one of the best conserved. The ability of the phosphoinositides to permeate both hydrophobic and hydrophilic environments, and their diverse functions within cells have contributed to their persistence in nature. In eukaryotes, phosphoinositides are essential metabolites as well as labile messengers that regulate cellular physiology while traveling within and between cells. The stereospecificity of the six hydroxyls on the inositol ring provides the basis for the functional diversity of the phosphorylated isomers that, in turn, generate a selective means of intracellular and intercellular communication for coordinating cell growth. Although such complexity presents a difficult challenge for bench scientists, it is ideal for the regulation of cellular functions in living organisms.