Two simple and sensitive spectrophotometric methods are described for the determination of ethionamide (ETM) in pure drug and tablets. The first method is based on the reduction of Folin-Ciocalteu (F-C) reagent by ETM in sodium carbonate medium to form a blue coloured complex, which was measured at 760 nm (Molybdenum-tungsten blue method). In the second method (Prussian blue method), iron (III) was reduced to iron (II) by ETM in HCl medium, the iron (II) formed was complexed with ferricyanide, and the resulting Prussian blue also measured at 760 nm. The absorbance measured in each case was related to ETM concentration. The experimental conditions were carefully studied and optimized. Beer's law was obeyed in the concentration ranges of 1–40 and 0.2–4.0 μg/ml with Molybdenum-tungsten blue method and Prussian blue method, respectively, with corresponding molar absorptivity values of 5.72 × 103 and 3.18 × 104 l/(mol.cm). The limits of detection (LOD) and quantification (LOQ) were 0.09 and 0.27 μg/ml (Molybdenum-tungsten blue method) and 0.01 and 0.04 μg/ml (Prussian blue method). Within-day and between-day relative standard deviations (%RSD) at three different concentration levels were