'Exercise on Prescription' (EoP) is used for initiating physical activity among sedentary patients with signs of lifestyle diseases. EoP is personalized secondary prevention in primary healthcare. This review addresses EoP using a Health Technology Assessment perspective and aims to answer the following questions: (1) Does EoP increase physical activity level or physical fitness, and is more intensive EoP more effective than less intensive? (2) Is EoP acceptable and feasible in general practice? (3) Is EoP acceptable to and feasible for sedentary patients? (4) Is EoP cost-effective? EoP studies were searched using Medline thesaurus topic, Medline WinSPIRS, reference lists of recent reviews, and NLM Gateway Locator plus. A total of 22 studies were included in the review. Most studies reported moderate improvements in physical activity or physical fitness for 6-12 months. Among patients receiving EoP 10% more had improved physical activity level compared with controls and mean aerobic fitness was improved by 5-10% among EoP patients compared with controls. Little evidence existed in support of the hypothesis that more intensive EoP is more effective. EoP was acceptable and feasible to GPs and patients volunteering for EoP. However, little is known about non-completers, patients declining EoP, and GPs not highly motivated for using EoP. Only one study addressed health economic issues. It found EoP cost-effective, but comparisons with other interventions have not been performed. Even though most studies in this review presented favourable results for EoP there is a lack of evidence in several fields. In particular we lack high-quality studies evaluating EoP schemes that are sustainable in everyday use in general practice.