Sometimes mistakenly characterized as a ‘universal antidote,’ activated charcoal (AC) is the most frequently employed method of gastrointestinal decontamination in the developed world. Typically administered as a single dose (SDAC), its tremendous surface area permits the binding of many drugs and toxins in the gastrointestinal lumen, reducing their systemic absorption. Like other decontamination procedures, the utility of SDAC attenuates with time, and, although generally safe, it is not free of risk. A large body of evidence demonstrates that SDAC can reduce the absorption of drugs and xenobiotics but most such studies involve volunteers and have little generalizability to clinical practice. Few rigorous clinical trials of SDAC have been conducted, and none validate or refute its utility in those patients who are intuitively most likely to benefit. Over the past decade, a growing body of observational data have demonstrated that SDAC can elicit substantial reductions in drug absorption in acutely poisoned patients. The challenge for clinicians rests in differentiating those patients most likely to benefit from SDAC from those in whom meaningful improvement is doubtful. This is often a difficult determination not well suited to an algorithmic approach. The present narrative review summarizes the data supporting the benefits and harms of SDAC, and offers pragmatic suggestions for clinical practice.