Tetrapyrrolic macrocycles, particularly meso-imidazolyl porphyrins and their chlorin derivatives, have gained significant attention as potent photosensitizers for antimicrobial photodynamic inactivation (aPDI). This chapter explores the synthetic methodologies to obtain two families comprising di-cationic and tetra-cationic imidazolyl porphyrins and chlorin derivatives. Their structure-activity relationships on aPDI, and broad-spectrum efficacy against Gram-positive and Gram-negative bacteria, biofilms, and viruses, including SARS-CoV-2 are discussed. The design of cationic imidazolyl porphyrins enhances bacterial uptake through electrostatic interactions, overcoming the structural barriers of bacterial membranes and biofilms. Studies highlight the superior efficacy of zinc-complexed tetra-cationic imidazolyl porphyrins in planktonic bacteria, while smaller, di-cationic derivatives demonstrate enhanced biofilm penetration and inactivation. In vivo studies confirm the effectiveness of chlorin-based photosensitizers in wound infection models, demonstrating significant bacterial load reduction with minimal cytotoxicity to host tissues. Additionally, the combination of aPDI with antibiotics, such as ciprofloxacin, and natural antimicrobial agents, such as cinnamaldehyde, significantly enhances therapeutic efficacy. The antiviral potential of these photosensitizers is also explored, with dicationic imidazolyl chlorins achieving near-total SARS-CoV-2 inactivation at low concentrations and light doses. These findings underscore the promising role of cationic imidazolyl porphyrins in developing innovative, light-activated antimicrobial and antiviral strategies, addressing the urgent need for effective treatments against multidrug-resistant pathogens.