At the present time photodynamic therapy (PDT) is receiving considerable interest for its potential as an antimicrobial therapy. This treatment may be a valuable tool in achieving a rapid reduction of the microbial burden perhaps even in the management of localized infections that are resistant to standard antibiotic regimens. A variety of photosensitizers from different groups including porphyrins, chlorophyll derivatives, phthalocyanines and azines have been effective in the photokilling of many Gram-positive and Gram-negative bacterial pathogens in addition to parasites, fungi, and viruses. Much of the suggested antimicrobial uses of this therapy are based on results from in vitro studies. Only a limited number of animal models of infection or clinical studies have been employed to assess the effectiveness of PDT. These studies have reported moderate successes that have not quite achieved the expectations projected from the in vitro results. In order to fully validate the potential of PDT as an antimicrobial therapy considerably more effort is required in the area of appropriate experimental models to better understand the mechanisms of photodynamic destruction of bacteria.