Muscle cramps can occur anywhere and in anyone; however, leg cramps are especially common in older people. Quinine is a medication which has been used to treat cramps for many years. There is conflicting evidence for its ability to reduce cramps. It can cause serious, even fatal adverse events, especially in overdosage. Twenty-three trials including 1586 participants were included in this review, comparing quinine or quinine derivatives against placebo or other interventions. There is moderate quality evidence that quinine significantly reduces cramp frequency, intensity and cramp days more than placebo. There is moderate quality evidence that there is a significant increase in minor adverse events with quinine compared to placebo but not in major adverse events. Overdosage however is well documented to cause serious harm including death. There is low quality evidence from one trial that theophylline combined with quinine improves cramps more than quinine alone. Low quality evidence shows there is no significant difference between quinine and vitamin E, quinine-vitamin E mixture, or xylocaine injections. More research is needed to clarify the optimum dose and duration of treatment, as well as alternatives to quinine.