The stage is set for a new era of precariousness in modern medicine, driven by the increasing failure of a key pharmaceutical pillar—antimicrobials. In the context of sexually transmitted infections (STIs), the rise of antimicrobial resistance is introducing urgent questions around what might constitute “best practice” in a rapidly evolving scene, including the value of asymptomatic screening (test and treat), and the consequent downstream collateral damage emerging from over-use of our diminishingly effective antimicrobial resources. Drawing on interviews with clinicians, experts, and industry representatives, we examine resistance as a site of emerging and co-constitutive moral, temporal, and economic dilemmas. Such dilemmas, as illustrated in participants’ accounts, involve complexities regarding prioritization between competing health demands; doing good work while meeting business requirements; considering trade-offs between visibility and amplifying the problem; difficulties balancing presents and futures; reconciling divergent clinical opinions and expertise; and managing patient subjectivities, while considering the implications of clinical practices for resistance. Importantly, centering dilemmas in context of antibiotic-resistant STIs open greater theoretical scope to consider the challenging spaces that key actors such as clinicians and decision-makers occupy, as they attempt to curb resistance while caring for individuals and the community.