Intracellular pH (pHi) plays many critical roles in cell, enzyme, and tissue activities, including proliferation and apoptosis, multi drug resistance (MDR), ion transport, endocytosis, and muscle contraction has been reported. Intimate connections between the cell functions with intracellular pH means that precise measurement of intracellular pH can provide critical information for studying physiological and pathological processes down to a single organelle. A variety of methods can be used for importing highly charged fluorescent compounds into cells. BCECF and BCPCF are preferred for intracellular pH measurements, but fluorescein, fluorescein sulfonic acid, and, especially, carboxyfluorescein are still widely used for pH determination presumably because they are easy and cheap to prepare via standard condensation methods. Probes for pHi measurements can be used to study pH i dependent biological and pathological processes, such as cell death, cancers, and cell proliferation.