Optimization models and algorithms have played a critical role in radiotherapy treatments of cancer since the advent of intensity modulated radiotherapy in the 1990s, perfecting both the mathematical models and computational methods used in standard radiotherapy modalities. This talk will focus on another family of questions aimed at moving beyond conventional treatment planning: how optimization models can help with the selection, and possible combination, of treatment modalities, and in determining the ideal dose prescriptions for patients through a concept called biologically effective dose.