There remains insufficient evidence to support the routine use of pharmacologic interventions in the treatment of POD. While the evidence supporting dexmedetomidine seems most promising, its clinical significance is questionable and therefore its impact is likely in prevention rather than treatment. Various methodological challenges, including heterogeneity in trial design and insufficient stratification by delirium subtype, hinder generalizability of study results and advancements in how delirium is understood. Future progress will depend on reconceptualizing delirium away from a purely descriptive condition and toward a heterogenous, biologically driven disorder.