In this review, we discuss the following interrelated topics: (1) pro-survival role of constitutive NO in glioblastomas and other malignancies; (2) basic principles of PDT and the cytotoxic reactive oxygen species (ROS) produced; (3) mechanism of iNOS/NO induction by PDT; (4) hyper-resistance to PDT elicited by upregulated iNOS/NO; (5) NO-dependent hyper-aggressiveness of PDT-surviving cells; (6) tumor-supporting bystander effects of upregulated iNOS/NO; and (7) pharmacologic approaches for limiting the anti-PDT effects of NO. Here, NOS2 is linked to neoplasm.