The objective of this paper is to assess the effectiveness of alfalfa ( Medicago sativa L.) improvement efforts over the last century, and with the advent of molecular biology, identify challenges for alfalfa improvement in the future. Yield trials conducted between 1986 and 1998 from around the US were used to compare yield and persistence of older alfalfa cultivars to those released in the 1990s. First and second harvest forage yield of recently released alfalfa cultivars were not improved over those of older cultivars. New cultivars had higher forage yield at fourth harvest, in early September, possibly due to a reduction in fall dormancy. Efforts to improve alfalfa persistence by breeding for improved disease resistance and greater winter hardiness also have not been effective at most locations. Use of molecular biology for alfalfa improvement depends upon identifying genes that control important agronomic traits that translate into greater yield, improved persistence, and enhanced forage quality. Few such genes have been identified in alfalfa, and their use might be complicated by the polyploid nature of this outcrossing species. The Medicago truncatula genome project is providing large amounts of sequence information, but little is known about the regulation of these genes and the function of their protein products in planta. Uncertainty exists regarding the effectiveness of transferring these genes to alfalfa to obtain a desired phenotype. Much remains to be done to identify key genes that determine agronomic performance of crop plants, including alfalfa, and to clarify mechanisms that regulate the expression of genes and the function(s) of their protein products under field conditions. Future efforts to improve agronomic performance of alfalfa will be enhanced by partnerships between public and private scientists because companies now dominate commercial release of new alfalfa cultivars.