Moxidectin is a macrocyclic lactone related to ivermectin used in horses and dogs for endoparasite treatment and prophylaxis. The clinical and neurological presentation of moxidectin toxicity in two dogs following inadvertent poisoning with a moxidectin-containing equine de-worming medication is reported here. In both the dogs, the predominant clinical signs were generalised tremors and ataxia. Moxidectin exerts its neurotoxic effects in mammals by potentiating the effect of γ-aminobutyric acid and, consistent with this, both the dogs demonstrated a poor response to treatment with diazepam. It would be more appropriate to avoid γ-aminobutyric acid agonists, such as benzodiazepines and barbiturates, in dogs with moxidectin toxicity and consider using anaesthetic agents with a different mode of action, such as propofol. The prognosis in dogs accidentally exposed to moxidectin-containing equine de-worming medication appears to be excellent if the cause of the neurotoxicity is correctly identified and the case is appropriately managed.