In the modern age of advanced surgical techniques and pharmacologic management, bacterial spinal infections (SIs) can be managed (either eradicated or suppressed) in many hosts. However, the optimal management of SIs may be limited by patient comorbidities, which do not allow for surgical management, or limited by antimicrobial options due to side effects, toxicities, or emerging drug resistance. In these settings, frank and honest discussion regarding risks and benefits of treatment should be pursued, including that the SI may be a terminal illness. In this case series, we present 3 patients who had bacterial SIs whose treatments were limited by the above-mentioned factors. Furthermore, each case presented challenges regarding optimal medical management of somatic and neuropathic pain associated with the SI.