Bovine colostrum, the first milk that cows produce after parturition, contains high levels of growth factors and immunomodulatory components. Some healthy and diseased individuals may gain health benefits by consuming bovine colostrum as a food supplement. This review provides a systematic, critical evaluation of the current state of knowledge in this area. Fifty-one eligible studies were identified from the following databases: Medline, Embase, Global Health, the Cochrane Library, and the Cumulative Index to Nursing and Allied Health Literature. Studies were heterogeneous with regard to populations, outcomes, and methodological quality, as judged by the Jadad assessment tool. Many studies used surrogate markers to study the effects of bovine colostrum. Studies suggesting clinical benefits of colostrum supplementation were generally of poor methodological quality, and results could not be confirmed by other investigators. Bovine colostrum may provide gastrointestinal and immunological benefits, but further studies are required before recommendations can be made for clinical application. Animal models may help researchers to better understand the mechanisms of bovine colostrum supplementation, the dosage regimens required to obtain clinical benefits, and the optimal methods for testing these effects in humans.