The rise in resistance to known antibiotics has made developing new approaches to combatting bacterial pathogens increasingly urgent. I will discuss work from my lab that aims to address this unmet need by bringing biophysical perspectives to the problem. For example, the mechanics of host-pathogen interactions represent an important yet largely understudied mechanism for regulating and disrupting pathogenesis. We have also begun to combine machine learning and morphometric studies to design screens for antibiotics with novel mechanisms of action. Finally, novel methods for single-cell analysis enable new insights into the heterogeneity of bacterial responses to antibiotics, which may in turn help improve their use in treating infections.