First do no harm’ is a fine principle; however, most medicines worth using have side effects, so it’s important that the prescriber can assess the risk/benefit ratio. This chapter provides examples of good advice (e.g. not to use NSAIDs in renal or liver impairment), overly cautious advice that may be flouted (e.g. cephalosporins in pencillin allergic patients) and advice that may appear overly cautious but should still be followed as there is a safer alternative (e.g.metformin in renal failure).