Despite the acceptance of PDT as efficient treatment for selected indications, there is still place for improvement. This research demonstrates the feasibility of using combination therapy and targeted drug delivery as two different strategies that improve PDT in two specific applications: age-related macular degeneration and treatment of localized prostate cancer. Using the chick chorioallantoic membrane model we were able to demonstrate that the administration of anti-angiogenic agents subsequent to PDT treatment results in a synergetic effect and maintains the vascular occlusion over a longer period of time. We also developed and optimized a PS prodrug sensitive to uPA. It was (i) activated by uPA in vitro and PC cells expressing uPA; (ii) not toxic to PC cells in the dark but lethal in combination with light; (iii) able to be activated and to accumulate sufficiently in PC tumors in vivo; and (iv) cured xenografted mice after appropriate dosage and irradiation.