Insulin therapy or intensification of insulin therapy commonly results in weight gain in both type 1 and type 2 diabetes. This weight gain can be excessive, adversely affecting cardiovascular risk profile. The spectre of weight gain can increase diabetic morbidity and mortality when it acts as a psychological barrier to the initiation or intensification of insulin, or affects adherence with prescribed regimens. Insulin-associated weight gain may result from a reduction of blood glucose to levels below the renal threshold without a compensatory reduction in calorie intake, a defensive or unconscious increase in calorie intake caused by the fear or experience of hypoglycaemia, or the ‘unphysiological’ pharmacokinetic and metabolic profiles that follow subcutaneous administration. There is, however, scope for limiting insulin-associated weight gain. Strategies include limiting dose by increasing insulin sensitivity through diet and exercise or by using adjunctive anorectic or insulin-sparing pharmacotherapies such as pramlintide or metformin. Insulin replacement regimens that attempt to mimic physiological norms should also enable insulin to be dosed with maximum efficiency. The novel acylated analogue, insulin detemir, appears to lack the usual propensity for causing weight gain. Elucidation of the pharmacological mechanisms underlying this property might help clarify the mechanisms linking insulin with weight regulation.