The epidemic of obesity and metabolic syndrome (MS) contributes to the rapid growth of chronic kidney disease (CKD) and end-stage renal disease (ESRD). There is a reverse epidemiology, known as the "obesity paradox," in ESRD patients receiving maintenance dialysis. Obese patients are routinely referred for kidney transplant, and they have more surgical and medical complications than non-obese patients. However, compared to dialysis, kidney transplant provides a survival benefit for obese patients. After kidney transplant, obese patients tend to gain more body weight, and non-obese patients can develop new-onset obesity/MS. Obesity/MS is not only associated with serious morbidities, but also compromises the long-term graft and patient survival. The immunosuppressive drugs commonly used as maintenance therapy, including corticosteroids, calcineurin inhibitors and mammalian target-of-rapamycin inhibitors, contribute to obesity/MS. Development of novel immunosuppressive drugs free of metabolic adverse effects is needed, so that the full potential and benefits of kidney transplantation can be realized.