Contrast in optical coherence tomography (OCT) images is often limited, particularly when pathological tissue is morphologically or optically similar to normal tissue. In recent years, there has been increasing interest in developing methods for enhancing OCT contrast. In general, contrast can be enhanced by the administration of passive or targeted exogenous contrast agents, or by exploiting linear and nonlinear techniques for sampling the endogenous molecular composition of tissue. Many exogenous agents, in addition to being targeted to specific cells and tissues, can also serve as multifunctional agents, delivering or facilitating therapy as well as providing enhanced contrast for imaging and localization. This paper and presentation will discuss novel OCT contrast enhancing methods designed to selectively identify tissues of interest.