Inhibition of renal glucose reabsorption by the inhibition of the Sodium Glucose Transporter 2 (SGLT2) has emerged as not only a practical way to lower glucose levels in patients with type 2 diabetes without increasing the risk of hypoglycaemia or weight gain, but also with the clear potential for vasculoprotective effects that are independent to the achieved glucose control. The strong expectation surrounding drugs of this class has led to a rapid expansion of their use. However, such exciting data should be tempered by the potential for adverse effects, as the first priority in our patients must be to minimise the potential for harm. It is clear that complete deficiency of SGLT2 in humans is not dangerous, and leads to a condition known as benign familial glycosuria. Consequently, subtotal blockade of SGLT2 that occurs during pharmacological inhibition is often considered equally benign. However, in the setting of diabetes, SGLT2 inhibition increases urine output proportional to glycosuria, resulting in troublesome polyuria and nocturia in some patients, especially those with bladder/pelvic floor/prostate dysfunction. SGLT2 inhibition increases the frequency of genital mycotic infections in both men and women, although both are readily treatable and rarely severe or recurrent. Curiously, urinary tract infects are not increased by SGLT2 inhibitors, possibly as increased urine flow/frequent bladder emptying offsets the effect of glycosuria. Recent data has also emerged that SGLT2 inhibition increases ketogenesis, and in some selected settings may be associated with ketoacidosis. For the most part, each of these adverse effects can be mitigated by judicious prescribing and treatment planning.