Despite recent advances in surgery, chemotherapy, and radiation treatment, survival of patients with advanced malignancy remains suboptimal. Photodynamic therapy (PDT) is now established as a clinical treatment modality for various diseases including cancer (Dougherty et al., 1998). PDT involves the combined action of a photosensitizer, visible light of an appropriate wavelength and molecular oxygen to produce reactive oxygen species (ROS) like singlet oxygen, a short-lived species with highly cytotoxic effect (Dougherty et al., 1998, Solban et al., 2005). In biological system, the generated ROS trigger a cascade of biochemical effects that result in cell death. Singlet oxygen is thought to be the main mediator of cellular death, involving apoptotic and necrotic responses within treated tumours and produces microvascular injury leading to inflammation and hypoxia. PDT effects are mediated not only through direct killing of tumour cells but also through indirect effects, which involve both the initiation of an immune response against tumour cells and the destruction of tumour neovasculature. Indeed, the vascular effect plays a critical role in the eradication of tumour by PDT as it may cause deprivation of life-sustaining nutrients and oxygen supply from the existing blood vessels of the surrounding tissue. This present chapter will focus on recent and significant advances and developments in targeting strategies in PDT with the emphasis on vascular target specificity.