Clofazimine (CFZ), a riminophenazine derivative and a crucial drug in the treatment of lepromatous leprosy, has been reintroduced clinically to treat multidrug-resistant tuberculosis. CFZ holds both antimycobacterial and anti-inflammatory properties. But, due to its highly hydrophobic, polar and photosensitive nature, it is challenging to extract and quantify the drug from different biological fluids and its pharmaceutical formulations. This has also hampered the pharmacokinetic evaluation of the CFZ. This article accentuates various analytical methods viz. Identification methods, titrimetric methods, spectrometric methods such as colorimetric, fluorometric, mass spectroscopy and UV/Vis spectroscopy, Chromatographic methods like paper chromatography, thin-layer chromatography, high-performance thin layer chromatography, high-performance liquid chromatography, liquid chromatography tandem mass spectrometry for the estimation of CFZ in bulk, biological fluids and its pharmaceutical formulations.