The glycopeptides vancomycin and teicoplanin are widely used, and indeed recommended for, the treatment of severe or resistant Gram-positive infections. Therapeutic drug monitoring is widely used for vancomycin but less commonly for teicoplanin, and remains controversial. We report the cost savings of a formulary decision to replace teicoplanin with daptomycin for the empiric treatment of complicated skin and soft tissue infections (CSSTIs), staphylococcal bacteraemia and hospital-acquired Gram-positive sepsis. In the Intensive Therapy Unit (ITU) we optimised treatment of serious Gram-positive infections by substituting teicoplanin with vancomycin administered by continuous infusion. Costs were calculated using British National Formulary (BNF) prices and costs for therapeutic drug monitoring. Daptomycin (350 mg/d) use was associated with a cost saving per 7 days of treatment of 86 pounds and vancomycin with 51 pounds (4 g/d) to 276 pounds (2 g/d) compared to the 600 mg teicoplanin dose. Our own formulary re-positioning of glyco/lipopeptides, i.e. the preferential use of vancomycin in the ITU and substitution of teicoplanin with daptomycin, is cost-effective and provides better therapeutic alternatives. Continuous vancomycin infusion in the ITU setting guarantees optimal dosing for severely ill patients. Daptomycin use on surgical and medical wards, apart from being marginally cheaper than teicoplanin, guarantees optimal dosing without the need for drug monitoring.