We describe the case of a patient with pancreatitis followed by intra-abdominal infection in which source control was not achieved. Antimicrobial therapy led to the emergence of resistance in multiple organisms through multiple population dynamics processes. While the initial insult was not due to infection, subsequent infections with resistant organisms contributed to a poor outcome for the patient. Though resistance evolution was a known risk, it was difficult to predict the next organism that would arise in the setting of antibiotic pressure and its resistance profile. This case illustrates the clinical challenge of antibiotic resistance that current approaches cannot readily prevent. LAY SUMMARY Why is antibiotic resistance management so complex? Distinct evolutionary processes unfold when antibiotic treatment is initiated that lead, separately and together, to the undesired outcome of antibiotic resistance. This clinical case exemplifies some of those processes and highlights the dire need for evolutionary risk assessments to be incorporated into clinical decision making.