Various endocrine hormones are used therapeutically but, owing to short circulating half-lives, they typically must be administered frequently and at high doses. To address this, Liu et al. fused human growth hormone (GH) and human leptin as functional domains into the complementarity-determining regions (CDRs) of the humanized therapeutic antibody trastuzumab. The resulting fusion proteins expressed in mammalian cells in good yields and maintained the biological activity of the native hormones. The GH–antibody and leptin–antibody fusions exhibited increased half-lives and notably extended activities in a GH-deficient rat model and a leptin-deficient obese mouse model, respectively.