Introduction: Type 1 diabetes mellitus is a chronic, progressive autoimmune disorder linked to numerous genetic and environmental factors. Insulin is the only treatment and preventative strategies do not currently exist. An obvious need exists to develop a safe regimen that suppresses the progression of the disease. Areas covered: A MEDLINE search (1966-June 2011) was conducted for English-language articles using the terms 'otelixizumab', 'anti-CD3 antibody' and 'prevention of type 1 diabetes mellitus'. Relevant literature on otelixizumab, an anti-CD3 monoclonal antibody, currently in Phase III clinical trials for prevention of T1DM is discussed. Expert opinion: Studies suggest that a monoclonal antibody directed against CD3 mitigates the deterioration in insulin production and decreases the rise in insulin requirement in recent onset T1DM for up to five years. The benefit was most pronounced in younger patients and in those with higher initial beta-cell function. Adverse effects were significant but transient. Otelixizumab shows great promise but leaves room for improvement. Results of ongoing trials will help define its role in the prevention of T1DM.