Two simple and sensitive methods to determine atorvastatin calcium (ATO) and pioglitazone hydrochloride (PIO), in tablet dosage form, were developed and validated using reverse phase liquid chromatography (LC) and high performance thin layer chromatography (TLC). The LC separation was achieved on a Phenomenex Luna C18 column (250mm, 4.6mm i.d., 5μm), in the isocratic mode using 0.65M ammonium acetate buffer: acetonitrile (50: 50 v/v), pH 6.9 ± 0.05, as the mobile phase at a flow rate of 1.2 mL/min. The retention times were about 4.64 and 6.39 min for ATO and PIO, respectively. Quantification was carried out at 258 nm over the concentration range of 0.5-3 μg/mL for each drug. The TLC separation was achieved on silica gel 60 F254 HPTLC plates using with acetone: benzene: acetic acid glacial (2.6 + 7.36 + 0.04 v/v/v), as the mobile phase. The Rf values were about 0.28 and 0.61 for ATO and PIO, respectively. Quantification was performed with ultraviolet (UV) detection at 258 nm over the concentration range of 50-300 ng/spot for each. Both methods were validated, and the results were compared statistically. They were found to be simple, specific, accurate and precise. The methods were successfully applied for the determination of ATO and PIO in tablet dosage form without any interference from common excipients.