This study critically reviews the effectiveness of exercise therapy and manual mobilisation in acute ankle sprains and functional instability by conducting a systematic review of randomised controlled trials. Trials were searched electronically and manually from 1966 to March 2005. Randomised controlled trials that evaluated exercise therapy or manual mobilisation of the ankle joint with at least one clinically relevant outcome measure were included. Internal validity of the studies was independently assessed by two reviewers. When applicable, relative risk (RR) or standardised mean differences (SMD) were calculated for individual and pooled data. In total 17 studies were included. In thirteen studies the intervention included exercise therapy and in four studies the effects of manual mobilisation of the ankle joint was evaluated. Average internal validity score of the studies was 3.1 (range 1 to 7) on a 10-point scale. Exercise therapy was effective in reducing the risk of recurrent sprains after acute ankle sprain: RR 0.37 (95% CI 0.18 to 0.74), and with functional instability: RR 0.38 (95% CI 0.23 to 0.62). No effects of exercise therapy were found on postural sway in patients with functional instability: SMD: 0.38 (95% CI -0.15 to 0.91). Four studies demonstrated an initial positive effect of different modes of manual mobilisation on dorsiflexion range of motion. It is likely that exercise therapy, including the use of a wobble board, is effective in the prevention of recurrent ankle sprains. Manual mobilisation has an (initial) effect on dorsiflexion range of motion, but the clinical relevance of these findings for physiotherapy practice may be limited.