The detection of retinal breaks is a key step in retinal detachment surgery. This chapter considers how vital stains might be used to enhance retinal break detection. Acid, basic, and neutral chromophores were used in the late 1930s and occasionally thereafter, but there are few reports on vital staining in the era of pars plana vitrectomy. One recent clinical study used a 41-gauge cannula to inject trypan blue into the subretinal space, in cases where no break could be identified by internal search. Heavy liquids were then used to vent the dye out of previously unseen retinal breaks, facilitating break detection. Laboratory studies of chromophores show that the degree and pattern of retinal staining depends on the characteristics of the chromophore - some dyes produce a linear, concentration-dependent increase in staining, others produce stepwise increments. Furthermore, the apparent hue of a dye may change with concentration and this may alter the color contrast with the predominantly red-orange background of the human fundus. Future studies may use fluorophore-tagged laboratory reagents to identify specific ocular tissues such as glia, interphotoreceptor matrix, retinal pigment epithelium, and devitalized tissue. These highly specific agents may facilitate vitreoretinal interventions other than retinal detachment surgery and there are many potentially exciting lines of inquiry.