Fluphenazine was the first oral antipsychotic medication to be formulated into a depot formulation. Two forms of the depot, a decanoate and an enanthate, are available. The decanoate is more commonly prescribed as it is likely to have fewer adverse effects (Marder et al., Psychopharmacol Bull 1990;26:256–259, 1990; Kurland and Richardson, Psychopharmacologia (Berl) 9:320–327, 1966). However, in comparison to the newer long-acting injectables (LAI), fluphenazine decanoate has been reported to cause greater extrapyramidal adverse effects and to significantly lower mood (Knights et al., Br J Psychiatry 135:515–523, 1979; Alarcon and Carney, Br Med J 3:564–567, 1969). This chapter provides clinical pearls on how to appropriately prescribe and administer fluphenazine decanoate.