Chapter 4 generalizes the concept of equivalent uniform dose (EUD) to hypoxic tumors and introduces a new concept of equivalent uniform aerobic dose (EUAD) that that is needed for analysis and optimization of treatment outcomes in radiotherapy for heterogeneous hypoxic tumors with 3D variable radiosensitivity. The concept of equivalent uniform dose (EUD) has been proven instrumental for the analysis of treatment outcomes and biological optimization of radiotherapy. However, the concept of EUD does not consider hypoxic tumors because it was developed for oxygenated tumors. The new concept of EUAD assumes that for any non-uniform distributions of the Oxygen Enhancement Ratio (OER) and radiation dose within a tumor, there is an equivalent uniform distribution of radiation dose under hypothetical aerobic conditions with OER=1 that produces equal survival of clonogenic cells.