Drug-induced immune hemolytic anemia is considered to be rare but is likely underrecognized. The consulting pathologist plays a critical role in integrating serologic findings with the clinical history, as drug-induced antibodies should be distinguished as either drug-dependent or drug-independent for appropriate clinical management. Drug-dependent antibodies (DDABs) are most commonly associated with cefotetan, ceftriaxone, and piperacillin, whereas fludarabine, methyldopa, β-lactamase inhibitors, and platinum-based chemotherapeutics are frequent causes of drug-independent antibodies (DIABs). DDABs usually demonstrate a positive direct antiglobulin test and a negative elution, while DIABs are serologically indistinguishable from warm autoantibodies and are similarly steroid-responsive. Drug cessation is always recommended.