Detection of neurotoxic metals in the intracellular milieu has made an important contribution to the understanding of the mechanism of metal-induced neuronal injury. Fluorescent, metal-sensitive dyes have proven to be valuable in the measurement of a variety of neurotoxic cations in neurons, and these dyes have provided a number of insights into the relationships between elevations in the cytosolic free-metal concentrations and neuronal death. However, the dyes also have important limitations that can make the interpretation of dye signals difficult. In this review, the characteristics of dyes that can be used to detect both iron and zinc inside neurons, and the methods necessary to distinguish these ions from other intracellular signals, are reviewed. Also provided are examples of the use of the dyes for the redox-sensitive detection of iron and zinc. Finally, the challenges facing the use of these dyes for quantitative determination of changes in intracellular free-ion concentrations are discussed.