Chronic microglial activation (CMA) has been observed in conjunction with neurodegeneration after traumatic brain injury (TBI), prompting researchers to explore CMA inhibition as a possible therapeutic strategy. In a randomized, open-label trial that was recently reported in Brain, David Sharp and colleagues examined the effects of the antibiotic minocycline on CMA and neurodegeneration in 15 patients who had sustained a TBI at least 6 months earlier. The investigators found that minocycline treatment reduced CMA but, somewhat surprisingly, was also associated with increases in brain atrophy and plasma levels of neurofilament light protein, both of which are indicative of neurodegeneration. These findings raise the prospect that microglial activation has a beneficial role after TBI, which might be harnessed to improve patient outcomes.