Ethylene glycol poisoning, while uncommon, is clinically significant due to the associated risk of severe morbidity or lethality and it continues to occur in many countries around the world. The clinical presentation of ethylene glycol toxicity, while classically described in three phases, varies widely and when combined with the range of differential diagnoses that must be considered makes diagnosis challenging. Early and accurate detection is important in these patients, however, as there is a need to start antidotal treatment early to prevent serious harm. In this article, we will review the literature and provide guidance regarding the diagnosis of ethylene glycol poisoning. While gas chromatography is the gold standard, the usefulness of this test is hampered by delays in access due to availability. Consequently, there are several surrogate markers that can give an indication of ethylene glycol exposure but these must be interpreted with caution and within the clinical context. An in-depth review of these tests, particularly the detection of a raised osmolar gap or an raised anion gap acidosis, will form the main focus of this article.