In recent years, there has been heightened interest in the B vitamin folic acid, initially through its role in reducing neural tube defects, such as spina bifida, and, more recently, through its relationship with homocysteine and consequently the beneficial role it would seem to play in occlusive vascular disease. In addition, its sphere of influence may extend beyond these important conditions to include several cancers, Alzheimer's disease and affective disorders. The beneficial effects of folate in the above conditions can be explained largely within the context of folate-dependent pathways, such as methionine, purine and pyrimidine biosynthesis. However, the precise detail of folate metabolism is extremely complex and difficult to study because folate-dependent one-carbon metabolism is compartmentalised, involves an enormous number of low-abundance, difficult-to-measure, highly labile folyl coenzymes, and is the subject of genetic variability. Here we integrate some of the most recent findings in the field to provide a new perspective on folate status and some of the varied mechanisms by which folate ameliorates disease.