Two sensitive and reproducible methods are described for the quantitative determination of zonisamide in the presence of its degradation products. The first method was based on high performance thin layer chromatographic (HPTLC) followed by densiometric measurements of their spots at 238 nm.the separation was on HPTLC aluminium sheets of silica gel 60 F254, using toluene:ethtyl acetate (6:4 v/v), this system was found to give compact spots for zonisamide after development (Rf value 0.49.). The second method based on high performance liquid chromatographic (HPLC) of the drug from its degradation products on reversed phase Vydac column ODS (250 mm × 4.6 mm, 5.0 µ), at ambient temperature using a mobile phase consisting of methanol: water (50:50, v/v) and Retention time was (4.71 min.) Both the methods were validated as ICH guidelines no chromatographic interference from capsule excipients was found. Zonisamide was subjected to acid and alkali hydrolysis, oxidation,and dry heat. The drug was fount to be stable in neutral wet heat and photo- degradation conditions as the proposed analytical methods could effectively separated the drug from its degradation products, they can be employed as stability-indicating.