To grow and progress, solid tumors develop a vascular network through co-option and angiogenesis that is characterized by multiple structural and functional abnormalities, which negatively influence therapeutic outcome through direct and indirect mechanisms. As such, the morphology and function of tumor blood vessels, plus their response to different treatments, are a vital and active area of biological research. Intravital microscopy (IVM) has played a key role in studies of tumor angiogenesis, and ongoing developments in molecular probes, imaging techniques, and postimage analysis methods have ensured its continued and widespread use. In this review we discuss some of the primary advantages and disadvantages of IVM approaches and describe recent technological advances in optical microscopy (e.g., confocal microscopy, multiphoton microscopy, hyperspectral imaging, and optical coherence tomography) with examples of their application to studies of tumor angiogenesis.