The American cranberry (Vaccinium macrocarpon Ait.) contains rich antioxidants and has significant health benefits in fighting a variety of human diseases. In the past ten years, cranberry growers have reported yellow vine syndrome, which is associated with reduced photosynthetic performance, in the cranberry bogs. It has been found that the yellow vine syndrome of cranberry is associated with nutritional imbalance; it might be an issue for cranberry quality and food security as well as the crop production. This review evaluates the present state of knowledge of yellow vine syndrome, together with recent advances that are resulting from an improved mechanistic understanding and a possible solution that will be of considerable value to cranberry growers. This review also includes results from the author’s own laboratory. Water stress, nutritional imbalance, and photoinhibition are the likely reasons for producing yellow vine of cranberry. Future endeavors should be placed on the combination of genetic, biochemical, and biophysical techniques at the molecular level and plant physiology at the field and greenhouse level. This may provide specific information in order to understand the molecular details of yellow vine of cranberry as well as a tool for guiding future breeding efforts and management practices