In March 2012, the Wyoming Department of Health was notified by Natrona County public health officials regarding three patients hospitalized for unexplained acute kidney injury (AKI), all of whom reported recent use of synthetic cannabinoids (SCs), sometimes referred to as “synthetic marijuana.” SCs are designer drugs of abuse typically dissolved in a solvent, applied to dried plant material, and smoked as an alternative to marijuana. AKI has not been reported previously in users of SCs and might be associated with 1) a previously unrecognized toxicity, 2) a contaminant or a known nephrotoxin present in a single batch of drug, or 3) a new SC compound entering the market.