Microbial resistance to antibiotics has become a major area of research having caused over a million human deaths in 2019. At present, lower respiratory infection is the most burdensome disease. Antimicrobial Photodynamic Therapy (PDT) is regularly reported not to cause resistance in any pathogen, and to eradicate both microbes that are susceptible to antibiotics and those that are resistant. However, evidence now suggests that resistance to photosensitiser drugs at low concentrations is possible, and that tolerance to the reactive oxygen species (ROS) created during subsequent light exposure will occur eventually. Additionally, an increased optical fluence and the addition of medication have been necessary to destroy antibiotic resistant strains of Staphylococcus Aureus. Research has mostly focussed on bacteria, though the importance of fungi is highlighted here given the ubiquity of clinical manifestations like mycosis and urinary tract infection. Proposed next steps are the definition of terminology and methodology for experiments on microbial resistance/tolerance to PDT, varying the photosensitiser used for repeat PDT while controlling oxygen and salt levels, and alternative treatments including the interception of neuroimmunological signalling. Similar to the ESKAPE ranking of antibiotic resistant pathogens, a list summarising the degree of microbial resistance to PDT may have a place.