Photodynamic therapy (PDT) is a relatively new treatment for malignant and non-malignant diseases and by now successfully employed in many clinical applications. It is typically carried out as a two-step protocol with target cells first being selectively loaded with a photosensitizer followed by irradiation with light of the appropriate wavelength. Subsequent photochemical reactions lead to the production of reactive oxygen species (ROS) and cell death. PDT can trigger both modes of cell death, apoptosis and necrosis in target cells. Apoptosis is an active, controlled and energy-requiring process and therefore contrasts necrosis, which is an entropic event and in most cases a consequence of loss of membrane integrity and metabolic homeostasis. Photodynamic therapy has been shown to effectively induce apoptosis in several model systems since ROS formed by photoprocesses can directly damage mitochondria, which act as key regulators in active cell death. Therefore PDT may be able to set off the apoptotic cascade even in those cells which were shown to be resistant to apoptosis in response to chemotherapy or ionizing radiation. The cell death mode after PDT is of interest since it influences the response of the immune system and therefore the effectiveness of the treatment: apoptotic as well as necrotic cell death influence the activity and the specific response of various cell types involved in potential antitumor response of the immune system. The mode of cell death triggered by PDT can be influenced by altering the treatment protocol and can lead to a desired apoptosis/ necrosis ratio most advantageous for complete tumor eradication.