Photodynamic therapy (PDT) appears to be endowed with several favourable features for the treatment of localized microbial infections, especially after the advent of cationic photosensitising agents (phenothiazines, meso-substituted porphyrins, polylysine-bound chlorins) which properly interact with the outer wall at the surface of several types of bacterial and yeast cells, increase their permeability, and allow significant amounts of photosensitizer to be accumulated at the level of the cytoplasmic membrane. These photosensitisers are characterized by a broad spectrum of activity, being effective toward both wild strain and antibiotic-resistant gram-positive and gram-negative bacteria and yeasts. In general, extensive eradication of pathogens can be achieved under mild irradiation conditions, such as short incubation times and low fluence-rates, which guarantees a high degree of selectivity in comparison with the main constituents of host tissues, such as keratinocytes and fibroblasts. Moreover, the photosensitised inactivation of microorganisms is typically a multi-target process; as a consequence, the selection of photoresistant microbial strains is very unlikely and has not been experimentally observed so far. Possible initial targets of antimicrobial PDT applications include periodontal diseases, impetigo, atopic dermatitis, acne vulgaris, infected wounds, and superinfected posriatic plaques.