Antimicrobial blue light (aBL; 400–420 nm) is increasingly explored as a non-antibiotic approach against drug-resistant bacteria. Due to its multitarget, reactive oxygen species (ROS)-mediated mechanism of action, aBL is generally considered unlikely to induce classical genetic resistance. However, experimental findings indicate that adaptive responses may arise under specific conditions. This chapter critically examines available studies assessing resistance and tolerance development following repeated aBL exposure. While most investigations using lethal doses and single-colony passaging report no stable resistance after multiple cycles, several studies applying sublethal regimens and population-based selection models demonstrate the emergence of stable tolerance phenotypes, often detectable after four to five cycles. Tolerance is associated with enhanced oxidative stress responses, activation of the SOS system, envelope remodeling, and mutagenic DNA repair pathways. Importantly, methodological differences, including dose selection, inoculum source, and stability testing, substantially influence outcomes and may explain discrepancies across reports. Although high-level resistance to aBL appears rare, sublethal exposure may promote physiological plasticity and tolerance. Careful protocol design and continued monitoring are therefore essential as aBL advances toward broader clinical use.