Abstract. All natural populations deal with multiple stressors. Yet there is limited understanding of how populations are impacted by higher-order — more than two stressors — interactions. In this talk I will explain my new conceptual and experimental work to examine higher-order interactions among antibiotics in bacterial populations. I will also present recent work from my group that shows bacteria likely co-opted ancient stress response mechanisms to extreme temperatures in order to deal with more recent antibiotic stresses. This co-opting avoids the need for de novo evolution of response mechanisms to antibiotics. Finally, I will describe ongoing research in my lab that highlights strategies for altering rates of adaptation, the meaning and applications of interaction landscapes, clinical and translational opportunities, as well as urban adaptation in birds.