Drug resistance is a multifactorial phenomenon studied in detail in microbiology where it evolves rapidly because of genetic promiscuity in bacteria. However, it is also a major problem in cancer therapeutics and shares some commonalities with our microbe relatives. Multidrug resistance (MDR) is a term used commonly in both fields and refers to several mechanisms of resistance. One of the primary ones is the development of efflux pumps that pump out or bind to therapeutics preventing them from acting at target sites. The development of antiapoptotic protein overexpression or DNA repair mechanisms are only some of the other mechanisms. Other mechanisms involve the development of preventing drug delivery or suppression of the immune response. This presentation will focus on how photodynamic activation can be used as a tool to overcome some of these pathways of drug resistance acquisition/induction and how it might be a unique tool in the armamentarium of combination cancer therapeutics.