Tumor oxygenation status is an independent prognostic indicator in cancer because it influences tumor progression and treatment outcome. Its quantitative value is determined by a number of tumor vascular parameters such as microvascular density, blood flow, blood volume, blood oxygen saturation, tumor tissue pO2, and resistance to oxygen diffusion within the tumor. Over the past several years, considerable time and effort have been invested into developing techniques to effectively and reliably measure the oxygenation status of a tumor. The measurement and interpretation of data obtained with currently available methods is complicated by the heterogeneity in tumor oxygenation. Currently available techniques can be broadly classified into direct invasive methods, direct non-invasive methods, and measurement of surrogate endogenous markers of tumor oxygenation. Of these methods, the Eppendorf pO2 histograph is considered the 'gold standard' and even so has several limitations. Given the importance of tumor oxygenation status in therapy and in predicting disease progression, it is imperative that reliable, globally usable, and technically simplistic methods be developed to yield a consistent, comprehensive, and reliable profile of tumor oxygenation. Until newer more reliable techniques are developed, existing independent techniques or appropriate combinations of techniques should be optimized and validated using known endpoints in tumor oxygenation status and/or treatment outcomes.