Microbial infection is a severe concern, requiring the use of significant amounts of antimicrobials/biocides, not only in the hospital setting, but also in other environments. The increasing use of antimicrobial drugs and the rapid adaptability of microorganisms to these agents, have contributed to a sharp increase of antimicrobial resistance. It is obvious that the development of new strategies to combat planktonic and biofilm-embedded microorganisms is required. Photodynamic inactivation (PDI) is being recognized as an effective method to inactivate a broad spectrum of microorganisms, including those resistant to conventional antimicrobials. In the last few years, the development and biological assessment of new photosensitizers for PDI were accompanied by their immobilization in different supports having in mind the extension of the photodynamic principle to new applications, such as the disinfection of blood, water, and surfaces. In this review, we intended to cover a significant amount of recent work considering a diversity of photosensitizers and supports to achieve an effective photoinactivation. Special attention is devoted to the chemistry behind the preparation of the photomaterials by recurring to extensive examples, illustrating the design strategies. Additionally, we highlighted the biological challenges of each formulation expecting that the compiled information could motivate the development of other effective photoactive materials.